Process for producing organotitanium compound and process for addition reaction

ABSTRACT

A process for producing an organotitanium compound capable of regioselectively converting a substituted acetylene compound into polysubstituted benzene or polysubstituted pyridine. The process comprises reacting an acetylene compound represented by the formula (1)  
                 
 
     [where R 1  and R 2  denote a C 1-20  alkyl group or the like] in the presence of a prescribed titanium compound and a Grignard reagent with a compound represented by the formula (4)  
                 
 
     [where R 3  and R 4  denote a hydrogen atom or the like] and further reacting with a compound represented by the formula (5)  
                 
 
     [where R 5  denotes a hydrogen atom or the like, Z denotes CR′ (where R′ denotes a hydrogen atom or the like), nitrogen atom, X 6  denotes a halogen atom or the like, and m is 0 or 1] 
     thereby giving the titanium compound represented by the formula (6) and/or (7).  
                 
 
     [where R 1 ˜R 5 , Z, X 6 , and m are defined as above; and X p  and X q  denote any of X 1 ˜X 4 ].

BACKGROUND OF THE INVENTION

[0001] The present invention relates to a process for producing anorganotitanium compound useful for production of pharmaceuticals andagricultural chemicals and their intermediates and also to a process foraddition reaction involving the organotitanium compound. Moreparticularly, the present invention relates to a process for producingan organotitanium compound useful for production of polysubstitutedbenzene or polysubstituted pyridine.

[0002] There is an established process known as Reppe reaction forproducing a benzene compound directly from three acetylene compounds inthe presence of a catalyst of transition metal catalyst. This reaction,however, has difficulty in producing a polysubstituted benzene compoundregioselectively from substituted acetylene compounds.

[0003] As for regioselective production of a substituted benzenecompound from three acetylene compounds, several processes are disclosedin Chem. Rev. 2000, 100, 2901-2915. These processes are based oncondensation of one molecule of diyne compound and one molecule ofacetylene compound. Nothing is mentioned about the process of producinga substituted benzene compound regioselectively from three molecules ofacetylene compound.

[0004] There is known a process for producing a pyridine compoundregioselectively from two acetylene compounds and one nitrile compound.(J. Chem. Soc., Dalton 1978, 1278-1282, J. Am. Chem. Soc. 2000, 122,4994-4995)

[0005] The process disclosed in the former literature has thedisadvantage of requiring an expensive cobalt complex and beingincapable of using two acetylene compounds of different kind. Theprocess disclosed in the latter literature has the disadvantage ofrequiring an expensive zirconium catalyst and also requiring two-stagereactions with different catalysts. Therefore, both processes are notsuitable for industrial production.

SUMMARY OF THE INVENTION

[0006] The present invention was completed in view of the foregoing.Accordingly, it is an object of the present invention to provide aprocess for producing an organotitanium compound capable ofregioselectively converting a substituted acetylene compound into apolysubstituted benzene compound or a polysubstituted pyridine compound.It is another object of the present invention to provide a process foraddition reaction to produce polysubstituted benzene and polysubstitutedpyridine through addition of an electrophilic reagent to theorganotitanium compound.

[0007] In order to achieve the above-mentioned object, the presentinventors carried out extensive studies, which led to the finding thatit is possible to produce an organotitanium compound from a titaniumreagent as a reaction product of a tetravalent titanium compound (whichis commercially inexpensive) and a Grignard reagent, the organotitaniumcompound being capable of converting three molecules of acetylenecompound, or one molecule of acetylene compound and one molecule ofdiyne compound, into a benzene compound regioselectively, or convertingtwo molecules of acetylene compound and one molecule of nitrile compoundinto a pyridine compound regioselectively. The present invention isbased on this finding.

[0008] The present invention provides the following.

[0009] [1] A process for producing an organotitanium compound whichcomprises reacting an acetylene compound represented by the formula (1)below in the presence of a titanium compound represented by the formula(2) below and a Grignard reagent represented by the formula (3) belowwith an acetylene compound represented by the formula (4) below andfurther reacting with a compound represented by the formula (5) below,thereby giving the titanium compound represented by the formula (6)and/or (7) below.

[0010] [where R¹ and R² denote mutually independently a C₁₋₂₀ alkylgroup {which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C ₁₋₆-alkylaminocarbonyl group, phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).]

TiX¹X²X³X⁴   (2)

[0011] [where X¹, X², X³, and X⁴ denote mutually independently a halogenatom, C₁₋₆ alkoxy group {which may be substituted with a phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, orphenyl group) or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenoxygroup), or naphthoxy group.]

RMgX⁵   (3)

[0012] [where R denotes a C₂₋₈ alkyl group having a hydrogen atom at theβ position, and X⁵ denotes a halogen atom.]

[0013] [where R³ and R⁴ denote mutually independently a hydrogen atom,C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkylamino-carbonyl group, phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R¹² (where R¹⁰,R¹¹, and R¹² are defined as above).]

[0014] [where R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group) or naphthyl group), phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ group {where R⁶ denotes a C₁₋₆ alkylgroup or phenyl group (which may be substituted with a halogen atom orC₁₋₆ alkyl group) and n denotes 1 or 2}, OSO₂R⁶ group (where R⁶ isdefined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkylgroup); and m denotes 0 or 1.]

[0015] [where R¹˜R⁵, Z, X⁶, and m are defined as above; and X^(p) andX^(q) denote any of X¹˜X⁴ (which are defined as above).]

[0016] [2] A process for producing an organotitanium compound whichcomprises reacting an acetylene compound represented by the formula (8)below in the presence of a titanium compound represented by the formula(2) below and a Grignard reagent represented by the formula (3) belowwith a compound represented by the formula (5) below, thereby giving thetitanium compound represented by the formula (9) and/or (10) below.

[0017] [where R¹ denotes a C₁₋₂₀ alkyl group {which may be substitutedwith a C₁₋₆ alkoxy group (which may be substituted with a phenyl group)or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆alkyl group or phenyl group)}, C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkyaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denote mutuallyindependently a halogen atom, C₁₋₆ alkyl group, or phenyl group); R⁴denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylamino-carbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylamino-carbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² are defined as above);and Y denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷ (where Z¹, Z³, Z⁴, Z⁵, and Z⁷denote mutually independently C═O or CR¹⁴R¹⁵

where R¹⁴ and R¹⁵ denote mutually independently a hydrogen atom or C₁₋₆alkyl group (which may be substituted with a C₁₋₆ alkoxy group (whichmay be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, andR⁹ are defined as above))

, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶

where R¹⁶ denotes a C₁₋₆ alkyl group (which may be substituted with aC₁₋₆ alkoxy group (which may be substituted with a phenyl group) orOSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined as above))

, or CR^(14′)R^(15′)

where R^(14′) and R^(15′) denote mutually independently a hydrogen atomor C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))

}.]

TiX¹X²X³X⁴   (2)

[0018] [where X¹, X², X³, and X⁴ denote mutually independently a halogenatom, C₁₋₆ alkoxy group {which may be substituted with a phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, orphenyl group), or a naphthyl group)}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), or naphthoxy group.]

RMgX⁵   (3)

[0019] [where R denotes a C₂₋₈ alkyl group having a hydrogen atom at theβ position, and X⁵ denotes a halogen atom.]

[0020] [where R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group), or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ {where R⁶ denotes a C₁₋₆ alkyl groupor phenyl group (which may be substituted with a halogen atom or C₁₋₆alkyl group) and n denotes 1 or 2}, OSO₂R⁶ (where R⁶ is defined asabove), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkyl group);and m denotes 0 or 1.]

[0021] [where R¹, R⁴, R⁵, Y, Z, X⁶, and m are defined as above; andX^(p) and X^(q) denote any of X¹˜X⁴ (which are defined as above).]

[0022] [3] A process for producing an organotitanium compound whichcomprises reacting an acetylene compound represented by the formula (1)below in the presence of a titanium compound represented by the formula(2) below and a Grignard reagent represented by the formula (3) belowwith a compound represented by the formula (11) below, thereby givingthe titanium compound represented by the formula (12) below.

[0023] [where R¹ and R² denote mutually independently a C₁₋₂₀ alkylgroup {which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R8R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkyaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R ¹² (where R¹⁰,R¹¹, and R¹² denote mutually independently a halogen atom, C₁₋₆ alkylgroup, or phenyl group).]

TiX¹X²X³X⁴   (2)

[0024] [where X¹, X², X³, and X⁴ denote mutually independently a halogenatom, C₁₋₆ alkoxy group {which may be substituted with a phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, orphenyl group), or a naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), or naphthoxy group).]

RMgX⁵   (3)

[0025] [where R denotes a C₂₋₈ alkyl group having a hydrogen atom at theβ position, and X⁵ denotes a halogen atom.]

[0026] [where R³ denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxygroup, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylamino-carbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylamino-carbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² are defined as above);R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group (whichmay be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Y′ denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷{where Z¹, Z³, Z⁴, Z⁵, and Z⁷ denote mutually independently C═O orCR¹⁴R¹⁵

where R¹⁴ and R¹⁵ denote mutually independently a hydrogen atom or C₁₋₆alkyl group (which may be substituted with a C₁₋₆ alkoxy group (whichmay be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, andR⁹ are defined as above))

, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶ (where R¹⁶denotes a C₁₋₆ alkyl group (which may be substituted with C₁₋₆ alkoxygroup (which may be substituted with a phenyl group)) or OSiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above)

, or CR^(14′)R^(15′)

where R^(14′) and R^(15′) denote mutually independently a hydrogen atom,C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))

}; X⁶ denotes a halogen atom, C₁₋₆ alkoxy group {which may besubstituted with a phenyl group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenyl group), or naphthyl group),phenoxy group (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆alkoxy group, or phenyl group), naphthoxy group, SO_(n)R⁶ {where R⁶denotes a C₁₋₆ alkyl group or phenyl group (which may be substitutedwith a halogen atom or C₁₋₆ alkyl group), and n denotes 1 or 2}, OSO₂R⁶(where R⁶ is defined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotesa C₁₋₆ alkyl group); and m denotes 0 or 1.]

[0027] [where R¹ to R³, R⁵, Y′, X⁶, and m are defined as above; andX^(p) and X^(q) denote any of X¹˜X⁴ (which are defined as above).]

[0028] [4] A process for producing an organotitanium compound whichcomprises reacting an acetylene compound represented by the formula (1)below in the presence of a titanium compound represented by the formula(2) below and a Grignard reagent represented by the formula (3) belowwith a compound represented by the formula (13) below, thereby givingthe titanium compound represented by the formula (14) below.

[0029] [where R¹ and R² denote mutually independently a C₁₋₂₀ alkylgroup {which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkyaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).]

TiX¹X²X³X⁴   (2)

[0030] [where X¹, X², X³, and X⁴ denote mutually independently a halogenatom, C₁₋₆ alkoxy group {which may be substituted with a phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, orphenyl group) or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), or naphthoxy group.]

RMgX⁵   (3)

[0031] [where R denotes a C₂₋₈ alkyl group having a hydrogen atom at theβ position, and X⁵ denotes a halogen atom.]

[0032] [where R′ denotes a hydrogen atom or C₁₋₂₀ alkyl group; and X⁶denotes a halogen atom, C₁₋₆ alkoxy group (which may be substituted witha phenyl group (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆alkoxy group, or phenyl group) or naphthyl group}, phenoxy group (whichmay be substituted with C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ group {where R⁶ denotes a C₁₋₆ alkylgroup or phenyl group (which may be substituted with a halogen atom orC₁₋₆ alkyl group), and n denotes 1 or 2}, OSO₂R⁶ (where R⁶ is defined asabove), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkyl group).]

[0033] [where R¹, R², R′, Z, and X⁶ are defined as above; and X^(p) andX^(q) denote any of X¹ to X⁴ (which are defined as above).]

[0034] [5] A process for producing an organotitanium compound as definedin any of [1] to [4] above, wherein the titanium compound istetra-i-propoxytitanium.

[0035] [6] A process for producing an organotitanium compound as definedin any of [1] to [5] above, wherein the Grignard reagent is an i-propylGrignard reagent.

[0036] [7] A process for addition reaction which comprises adding to theorganotitanium compound obtained by the process defined in any of [1] to[6] above a compound having an electrophilic functional group or anelectrophilic reagent, and performing addition reaction on theorganotitanium compound.

[0037] [8] A process for addition reaction as defined in [7] above,wherein the electrophilic functional group is an aldehyde group, ketonegroup, imino group, hydrazone group, aliphatic double bond, aliphatictriple bond, acyl group, ester group, or carbonate group.

[0038] [9] A process for addition reaction as defined in [7] above,wherein the electrophilic reagent is water, heavy water, chlorine,bromine, iodine, N-bromosuccinimide, oxygen, carbon dioxide gas, orcarbon monoxide.

DETAILED DESCRIPTION OF THE INVENTION

[0039] The invention will be described in more detail in the following.Incidentally, throughout this specification, “n” implies “normal”, “i”implies “iso”, “s” implies “secondary”, “t” implies “tertiary”, “c”implies “cyclo”, “o” implies “ortho”, “m” implies “meta”, and “p”implies “para”.

[0040] (A) Process For Producing Organotitanium Compound

[0041] In the acetylene compound represented by the formula (1), R¹ andR² denote mutually independently a C₁₋₂₀ alkyl group {which may besubstituted with a C₁₋₆ alkoxy group (which may be substituted with aphenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ denote mutuallyindependently a C₁₋₆ alkyl group or phenyl group)}, C₃₋₂₀ alkenyl group,C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonylgroup, di-C₁₋₆-alkyaminocarbonyl group, phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).

[0042] The C₁₋₂₀ alkyl group may be a straight, branched, or cyclic one.It includes, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl,i-butyl, s-butyl, t-butyl, n-pentyl, c-pentyl, n-hexyl, c-hexyl,n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl,n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl,n-nonadecyl, and eicosanyl. It also includes those substituted alkylgroups, such as 2-methoxyethyl, 2-ethoxyethyl, 2-benzyloxyethyl,2-trimethylsiloxyethyl, 2-t-butyldimethylsiloxyethyl,2-t-butyldiphenylsiloxyethyl, 3-methoxypropyl, 3-ethoxypropyl,3-benzyloxypropyl, 3-trimethylsiloxypropyl,3-t-butyldimethylsiloxypropyl, 3-t-butyldiephenylsiloxypropyl,4-methoxybutyl, 4-ethoxybutyl, 4-benzyloxybutyl, 4-trimethylsiloxybutyl,4-t-butyldimethylsiloxybutyl, and 4-t-butyldiphenylsiloxybutyl.

[0043] Of these examples, favorable ones are methyl, ethyl, n-propyl,n-butyl, n-pentyl, n-hexyl, 2-methoxyethyl, 2-ethoxyethyl,2-benzyloxyethyl, 2-trimethylsiloxyethyl, 2-t-butylmethylsiloxyethyl,and 2-t-butyldiphenylsiloxyethyl. Particularly favorable ones aremethyl, n-butyl, n-hexyl, 2-bentyloxyethyl, and2-t-butyldimethylsiloxyethyl.

[0044] The C₃₋₂₀ alkenyl group may be a straight, branched, or cyclicone. It includes, for example, allyl, 2-butenyl, 3-butenyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,6-heptenyl, 7-octenyl, 3,7-dimethyl-6-octenyl, 8-nonenyl, 9-decenyl,10-undecenyl, 11-dodecenyl, 12-tridecenyl, 13-tetradecenyl,14-pentadecenyl, 15-hexadecenyl, 16-heptadecenyl, 17-octadecenyl,18-nonadecenyl, and 19-eicosenyl. Of these examples,3,7-dimethyl-6-octenyl is favorable.

[0045] The C₁₋₆ alkoxy group may be a straight, branched, or cyclic one.It includes, for example, methoxy, ethoxy, n-propoxy, i-propoxy,c-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, c-butoxy,1-methyl-c-propoxy, 2-methyl-c-propoxy, pentoxy, c-pentoxy, hexoxy, andc-hexoxy. Of these examples, favorable ones are methoxy, ethoxy,n-butoxy, c-pentoxy, n-hexoxy, and c-hexoxy. c-Hexoxy is particularlyfavorable.

[0046] The C₁₋₆ alkoxycarbonyl group is not specifically restricted solong as it is a carbonyl group having the above-mentioned C₁₋₆ alkoxygroup. It includes, for example, methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl,i-butoxycarbonyl, t-butoxycarbonyl, t-amyloxycarbonyl, vinyloxycarbonyl,allyloxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl,2,2,2-trichloroethoxycarbonyl, pentoxycarbonyl, and hexoxycarbonyl. Ofthese examples, favorable ones are methoxycarbonyl, ethoxycarbonyl,n-butoxycarbonyl, and t-butoxycarbonyl, and particularly favorable onesare ethoxycarbonyl and t-butoxycarbonyl.

[0047] The C₁₋₆ alkyl group may be a straight, branched, or cyclic one.It includes, for example, methyl, ethyl, n-propyl, i-propyl, c-propyl,n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl,2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl,3-methyl-n-butyl, 1,1-dimethyl-n-propyl, 1,2-dimethyl-n-propyl,2,2-dimethyl-n-propyl, 1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl,2-methyl-c-butyl, 3-methyl-c-butyl, 1,2-dimethyl-c-propyl,2,3-dimethyl-c-propyl, 1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl,1-methyl-n-pentyl, 2-methyl-n-pentyl, 3-methyl-n-pentyl,4-methyl-n-pentyl, 1,1-dimethyl-n-butyl, 1,2-dimethyl-n-butyl,1,3-dimethyl-n-butyl, 2,2-dimethyl-n-butyl, 2,3-dimethyl-n-butyl,3,3-dimethyl-n-butyl, 1-ethyl-n-butyl, 2-ethyl-n-butyl,1,1,2-trimethyl-n-propyl, 1,2,2-trimethyl-n-propyl,1-ethyl-1-methyl-n-propyl, 1-ethyl-2-methyl-n-propyl, c-hexyl,1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl,1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1,2-dimethyl-c-butyl,1,3-dimethy-c-butyl, 2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl,2,4-dimethyl-c-butyl, 3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl,2-n-propyl-c-propyl, 1-i-propyl-c-propyl, 2-i-propyl-c-propyl,1,2,2-trimethyl-c-propyl, 1,2,3-trimethyl-c-propyl,2,2,3-trimethyl-c-propyl, 1-ethyl-2-methyl-c-propyl,2-ethyl-i-methyl-c-propyl, 2-ethyl-2-methyl-c-propyl, and2-ethyl-3-methyl-c-propyl.

[0048] The C₁₋₆ alkylaminocarbonyl group and di-C₁₋₆-alkyl-aminocarbonylgroup are not specifically restricted so long as they are(di)alkylaminocarbonyl groups having the above-mentioned C₁₋₆ alkylgroup on the nitrogen atom. They include, for example,(di)methylaminocarbonyl, (di)ethylaminocarbonyl,(di)propylaminocarbonyl, and (di)butylaminocarbonyl. Of these examples,favorable ones are (di)methylaminocarbonyl, (di)ethylaminocarbonyl, and(di)n-propylaminocarbonyl. Particularly favorable one is(di)ethylaminocarbonyl.

[0049] The phenyl group includes, for example, phenyl, o-methylphenyl,m-methylphenyl, p-methylphenyl, p-ethylphenyl, p-i-propylphenyl,p-t-butylphenyl, o-methoxyphenyl, p-methoxyphenyl, 3,5-dimethylphenyl,3,5-dimethoxyphenyl, 3,5-diethylphenyl, 3,5-di-i-propylphenyl,2,4,6-trimethylphenyl, and 2,4,6-trimethoxyphenyl. Of these examples,phenyl is favorable.

[0050] The SiR⁷R⁸R⁹ group is not specifically restricted so long as itssubstituent groups (any of R⁷, R⁸, and R⁹) are mutually independently aC₁₋₆ alkyl group or phenyl group. It includes, for example,trimethylsilyl, triethylsilyl, truisopropylsilyl, tributylsilyl,t-butyldimethylsilyl, t-butyldiphenylsilyl, diphenylmethylsilyl, andtriphenyl-silyl. Of these examples, favorable ones are trimethylsilyl,t-butyldimethylsilyl, and t-butyldiphenylsilyl. Particularly favorableones are trimethylsilyl and t-butyldimethylsilyl.

[0051] The SnR¹⁰R¹¹R¹² group is not specifically restricted so long asits substituent groups (any of R¹⁰, R¹¹, and R¹²) are mutuallyindependently a halogen atom, C₁₋₆ alkyl group, or phenyl group. Itincludes, for example, trimethyltin, triethyltin, tributyltin,trichlorotin, and triphenyltin. Of these examples, favorable ones aretrimethyltin, triphenyltin, and trichlorotin.

[0052] Incidentally, the halogen atom may be any of fluorine, chlorine,bromine, and iodine.

[0053] In the titanium compound represented by the formula (2) above,X¹, X², X³, and X⁴ denote mutually independently a halogen atom, C₁₋₆alkoxy group {which may be substituted with a phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group)or naphthyl group}, phenoxy group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenoxy group), or naphthoxy group.

[0054] The C₁₋₆ alkoxy group includes (in addition to theabove-exemplified alkoxy groups) benzyloxy, o-methylbenzyloxy,m-methylbenzyloxy, p-methylbenzyloxy, o-methoxybenzyloxy,p-methoxybenzyloxy, phenethyloxy, o-methylphenethyloxy,m-methylphenethyloxy, p-methylphenethyloxy, o-methoxyphenethyloxy,p-methoxyphenethyloxy, 3-pheylpropoxy, 4-phenylbutoxy, 5-phenylpentoxy,6-phenylhexoxy, α-naphthylmethoxy, β-naphthylmethoxy,o-biphenylylmethoxy, m-biphenylylmethoxy, p-biphenylylmethoxy,a-naphthylethoxy, β-naphthylethoxy, o-biphenylylethoxy,m-biphenylylethoxy, and p-biphenylylethoxy. Of these examples, favorableones are methoxy, ethoxy, n-propoxy, i-propoxy, and n-butoxy.

[0055] The phenoxy group or naphthoxy group is not specificallyrestricted; it includes, for example, phenoxy, o-methylphenoxy,m-methylphenoxy, p-methylphenoxy, p-ethylphenoxy, p-i-propylphenoxy,p-t-butylphenoxy, o-methoxyphenoxy, p-methoxyphenoxy, α-naphthoxy,β-naphthoxy, o-biphenyloxy, m-biphenyloxy, and p-biphenyloxy.

[0056] The halogen atom X is not specifically restricted as mentionedabove. A favorable halogen is chlorine.

[0057] Incidentally, the C₁₋₆ alkyl group is defined as above.

[0058] Typical examples of the titanium compound includetetra-i-propoxytitanium, chlorotri-i-propoxytitanium, anddichlorodi-i-propoxytitanium. Of these examples, tetra-i-propoxytitaniumis favorable.

[0059] In the Grignard reagent represented by the formula (3) above, Rdenotes a C₂₋₈ alkyl group having a hydrogen atom at the β position, andX⁵ denotes a halogen atom.

[0060] R (which is a C₂₋₈ alkyl group having a hydrogen atom at the βposition) may be a straight, branched, or cyclic alkyl group which isnot specifically restricted so long as it has a hydrogen atom at the βposition. It includes, for example, ethyl, n-propyl, i-propyl, c-propyl,n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl,2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl,3-methyl-n-butyl, 1,1-dimethyl-n-propyl, 1,2-dimethyl-n-propyl,1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl, 2-methyl-c-butyl,3-methyl-c-butyl, 1,2-dimethyl-c-propyl, 2,3-dimethyl-c-propyl,1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl, 1-methyl-n-pentyl,2-methyl-n-pentyl, 3-methyl-n-pentyl, 4-methyl-n-pentyl,1,1-dimethyl-n-butyl, 1,2-dimethyl-n-butyl, 1,3-dimethyl-n-butyl,2,3-dimethyl-n-butyl, 3,3-diemthyl-n-butyl, 1-ethyl-n-butyl,2-ethyl-n-butyl, 1,1,2-trimethyl-n-propyl, 1-ethyl-l-methyl-n-propyl,1-ethyl-2-methyl-n-propyl, c-hexyl, 1-methyl-c-pentyl,2-methyl-c-pentyl, 3-methyl-c-pentyl, 1-ethyl-c-butyl, 2-ethyl-c-butyl,3-ethyl-c-butyl, 1,2-dimethyl-c-butyl, 1,3-dimethyl-c-butyl,2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl, 2,4-dimethyl-c-butyl,3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl, 2-n-propyl-c-propyl,1-i-propyl-c-propyl, 2-i-propyl-c-propyl, 1,2,2-trimethyl-c-propyl,1,2,3-trimethyl-c-propyl, 2,2,3-trimethyl-c-propyl,1-ethyl-2-methyl-c-propyl, 2-ethyl-1-methyl-c-propyl,2-ethyl-2-methyl-c-propyl, 2-ethyl-3-methyl-c-propyl, n-heptyl,5-methyl-n-hexyl, c-heptyl, n-octyl, 6-methyl-n-heptyl, and c-octyl. Ofthese examples, favorable ones are ethyl, n-propyl, i-propyl, n-butyl,and i-butyl.

[0061] The halogen atom (X⁵) is not specifically restricted. Favorableones are chlorine and bromine.

[0062] Typical examples of the Grignard reagent include ethyl Grignardreagent (such as ethyl magnesium chloride and ethyl magnesium bromide),n-propyl Grignard reagent (such as n-propyl magnesium chloride andn-propyl magnesium bromide), and i-propyl Grignard reagent (such asi-propyl magnesium chloride and i-propyl magnesium bromide). Of theseexamples, a favorable one is i-propyl Grignard reagent.

[0063] In the acetylene compound represented by the formula (4) above,R³ and R⁴ denote mutually independently a hydrogen atom, C₁₋₂₀ alkylgroup, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkylamino-carbonyl group, phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R¹² (whereR¹⁰R¹¹, and R¹² are defined as above).

[0064] The C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonylgroup, C₁₋₆ alkylaminocarbonyl group, di-C₁₋₆-alkylaminocarbonyl group,SiR⁷R⁸R⁹ group, and SnR¹⁰R¹¹R¹² group are the same as those defined inthe acetylene compound represented by the formula (1) above.

[0065] In the compound represented by the formula (5) above, R⁵ denotesa hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group) or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ group {where R⁶ denotes a C₁₋₆ alkylgroup or phenyl group (which may be substituted with a halogen atom orC₁₋₆ alkyl group) and n denotes 1 or 2}, OS_(n)R⁶ group (where R⁶ isdefined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkylgroup); and m denotes 0 or 1.

[0066] The SO_(n)R⁶ group is not specifically restricted; it includes,for example, methanesulfinyl, p-toluenesulfinyl,p-trifluoromethanesulfinyl, methanesulfonyl, benzenesuflonyl,p-toluenesulfonyl, and p-trifluoromethanesulfonyl. Of these examples,favorable ones are p-toluenesulfonyl and p-toluenesulfinyl.

[0067] The OSO₂R⁶ group is not specifically restricted; it includes, forexample, methanesulfonyloxy, benzenesufonyloxy, p-toluenesulfonyloxy,and p-trifluoromethanesulfonyloxy groups. Of these examples, a favorableone is p-toluene-sulfonyloxy group.

[0068] The OP(O)(OR¹³)₂ group is not specifically restricted; itincludes, for example, dimethyl phosphate, diethyl phosphate, anddiphenyl phosphate. Of these example, a favorable one is diethylphosphate.

[0069] Incidentally, the C₁₋₂₀ alkyl group, phenyl group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkylaminocarbonyl group, halogen atom, C₁₋₆ alkoxy group,phenoxy group, and naphthoxy group are the same as those defined above.

[0070] In the diyne compound in the formula (8) above, the terminalsubstituent groups R¹ and R⁴ are also defined as above.

[0071] Y denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷ {where Z¹, Z³, Z⁴, Z⁵, and Z⁷denote mutually independently C═O or CR¹⁴R¹⁵

where R¹⁴ and R¹⁵ denote mutually independently a hydrogen atom or C₁₋₆alkyl group (which may be substituted with a C₁₋₆ alkoxy group (whichmay be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, andR⁹ are defined as above))

, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶

where R¹⁶ denotes a C₁₋₆ alkyl group (which may be substituted with aC₁₋₆ alkoxy group (which may be substituted with a phenyl group) orOSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined as above))

, or CR^(14′)R^(15′)

where R^(14′) and R^(15′) denote mutually independently a hydrogen atom,C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))

}.

[0072] Y is not specifically restricted; it includes, for example,(CH₂)₃,(CH₂)₄, CH₂C(CH₂OCH₂Ph )₂CH₂, CH₂C(CH₂OSiMe₃)₂CH₂,CH₂C(CH₂OSit-BuMe₂)₂CH₂, CH₂C(CH₂OCH₃)₂CH₂, CH₂OCH₂, CH₂SCH₂,CH₂C(O)CH₂, C(O)N(CH₂Ph)CH₂, C(O)N(CH₃)CH₂, C(O)N(CH₂Ph)C(O), andC(O)N(CH₃)C(O). Of these examples, favorable ones are (CH₂)₃,CH₂C(CH₂OCH₂Ph)₂CH₂, and C(O)N(CH₂Ph)CH₂. Me stands for a methyl group,Ph stands for a phenyl group, and t-Bu stands for a t-butyl group.

[0073] In the compound represented by the formula (11) or (13), R³, R⁵,R′, and X⁶ are defined as above. Y′ is the same as Y mentioned above.

[0074] A mention is given below of the process for producing theorganotitanium compound represented by the formula (6) and/or (7).

[0075] The process consists of reacting an acetylene compoundrepresented by the formula (1) in the presence of a titanium compoundrepresented by the formula (2) and a Grignard reagent represented by theformula (3) with a compound represented by the formula (4) and furtherreacting with a compound represented by the formula (5), thereby givingthe titanium compound represented by the formula (6) and/or (7) above.

[0076] The molar amount of the titanium compound used in this reactionshould be 0.01-5 times, preferably 0.5-2 times, the amount of theacetylene compound (as the substrate) represented by the formula (1).The molar amount of the Grignard reagent should be 1-10 times the amountof the titanium compound used. The amount should be limited to 1.5-2.5times in order to avoid side reactions with the substrate.

[0077] The reaction may be carried out by adding the reactants in anyorder. One procedure involves mixing the titanium compound and theGrignard reagent and then adding to the mixture the acetylene compound(as the substrate) represented by the formula (1). Another procedureinvolves adding the titanium compound to the acetylene compoundrepresented by the formula (1), and then adding the Grignard reagent.Either procedure will do.

[0078] The molar amount of the compound represented by the formula (4)should be 0.5-2 times, preferably 0.6-1.2 times, the amount of theacetylene compound represented by the formula (1).

[0079] The molar amount of the compound represented by the formula (5)should be 0.5-2 times, preferably 0.8-1.5 times, the amount of theacetylene compound represented by the formula (1).

[0080] The solvent used in the reaction is not specifically restrictedso long as it is not involved in the reaction. It includes, for example,aromatic hydrocarbons (such as benzene, toluene, xylene, mesitylene,chlorobenzene, and o-dichlorobenzene), aliphatic hydrocarbons (such asn-hexane, cyclohexane, n-octane, and n-decane), halogenated hydrocarbons(such as dichloromethane, dichloroethane, chloroform, and carbontetrachloride), and ethers (such as tetrahydrofuran, diethyl ether,t-butyl methyl ether, and dimethoxyethane). Of these examples, favorableones are dichloromethane, tetrahydrofuran, and diethyl ether. They maybe used alone or in combination with one another.

[0081] The reaction temperature is not specifically restricted; it mayrange from −100° C. to the boiling point of the solvent. Preferredreaction temperatures are within the range from −80° C. to 40° C. Thereaction time is usually 0.1 to 1000 hours.

[0082] The above-mentioned reaction gives rise to the organotitaniumcompound represented by the above-mentioned formula (6) and/or (7). Thiscompound is unstable out of the reaction system. Therefore, it is notisolated as such. Instead, the reaction system is given an electrophilicreagent to bring about addition reaction at the titanium bondingposition, and the resulting addition product is isolated afterwards.

[0083] After the reaction is complete, the reaction system is given anaqueous solution of alkali to produce an aromatic compound in which ahydrogen atom is added to the titanium bonding position. Subsequently,this aromatic compound is extracted with an adequate solvent, and thereis obtained a crude product upon condensation under reduced pressure. Ifnecessary, the crude product is purified in the usual way bydistillation, recrystallization, silica gel column chromatography, orthe like. In this way it is possible to isolate the addition product inpure form.

[0084] It is presumed that the organotitanium compound represented bythe formula (6) or (7) is formed by the following reaction mechanism.

[0085] The titanium compound and the Grignard reagent give rise to adivalent titanium complex, which reacts with the first acetylenecompound represented by the formula (1) to give a titanacyclopropeneintermediate. This intermediate reacts with the second acetylenecompound represented by the formula (4) to give a titanacyclopendadieneintermediate. Between this intermediate and the compound represented bythe formula (5) occurs cyclic addition reaction. This addition reactioneliminates the leaving group, thereby giving rise to the organotitaniumcompound represented by the formula (6) or (7).

[0086] It is presumed that the ratio in which the above-mentionedorganotitanium compound is formed (or the orientation of the cyclicaddition reaction) varies depending mainly on the electron-attractingproperty of the substituent group at the 1- and 4-position of thecyclopentadiene intermediate.

[0087] A mention is made below of the process for producing theorganotitanium compound represented by the formulas (9) and/or (10)above.

[0088] The diyne compound represented by the formula (8) is reacted withthe compound represented by the formula (4) above in the presence of thetitanium compound represented by the formula (2) above and the Grignardreagent represented by the formula (3) above. The resulting reactionproduct is further reacted with the compound represented by the formula(5) to give the organotitanium compound represented by the formulas (9)and/or (10) above.

[0089] The molar amount of the titanium compound used in this reactionis 0.01-5 times, preferably 0.5-2 times, the amount of the diynecompound (as the substrate) represented by the formula (8). The molaramount of the Grignard reagent should be 1-10 times the amount of thetitanium compound used. The amount should be limited to 1.5-2.5 times inorder to avoid side reactions with the substrate.

[0090] The reaction may be carried out by adding the reactants in anyorder. One procedure involves mixing the titanium compound and theGrignard reagent and then adding to the mixture the diyne compound (asthe substrate) represented by the formula (8). Another procedureinvolves adding the titanium compound to the diyne compound representedby the formula (8), and then adding the Grignard reagent. Eitherprocedure will do.

[0091] The molar amount of the compound represented by the formula (5)should be 0.5-2 times, preferably 0.8-1.5 times, the amount of the diynecompound represented by the formula (8).

[0092] The solvent used in the reaction is not specifically restrictedso long as it is not involved in the reaction. It includes those whichhave been listed above.

[0093] The reaction temperature is not specifically restricted; it mayrange from −100° C. to the boiling point of the solvent. Preferredreaction temperatures are within the range from −80° C. to 40° C. Thereaction time is usually 0.1 to 1000 hours.

[0094] The above-mentioned reaction gives rise to the organotitaniumcompound represented by the above-mentioned formula (9) and/or (10).This compound is unstable out of the reaction system. Therefore, it isnot isolated as such. Instead, the reaction system is given anelectrophilic reagent to bring about addition reaction at the titaniumbonding position, and the resulting addition product is isolatedafterwards.

[0095] It is presumed that the organotitanium compound represented bythe formula (9) or (10) is formed by the following reaction mechanism.The reaction mechanism is identical with that mentioned above, exceptthat two molecules of the acetylene compounds represented by theformulas (1) and (4) are replaced by the diyne compound represented bythe formula (8).

[0096] A mention is made below of the process for producing theorganotitanium compound represented by the formulas (12) above.

[0097] The diyne compound represented by the formula (11) is reactedwith the acetylene compound represented by the formula (1) above in thepresence of the titanium compound represented by the formula (2) aboveand the Grignard reagent represented by the formula (3) above. In thisway it is possible to produce the organotitanium compound represented bythe formula (12) above.

[0098] The molar amount of the titanium compound used in this reactionis 0.01-5 times, preferably 0.5-2 times, the amount of the acetylenecompound (as the substrate) represented by the formula (1). The molaramount of the Grignard reagent should be 1-10 times the amount of thetitanium compound used. The amount should be limited to 1.5-2.5 times inorder to avoid side reactions with the substrate.

[0099] The reaction may be carried out by adding the reactants in anyorder. One procedure involves mixing the titanium compound and theGrignard reagent and then adding to the mixture the acetylene compound(as the substrate) represented by the formula (1). Another procedureinvolves adding the titanium compound to the acetylene compoundrepresented by the formula (1), and then adding the Grignard reagent.Either procedure will do.

[0100] The molar amount of the diyne compound represented by the formula(11) is 0.5-2 times, preferably 0.8-1.5 times, the amount of theacetylene compound represented by the formula (1).

[0101] The solvent used in the reaction is not specifically restrictedso long as it is not involved in the reaction. It includes those whichhave been listed above.

[0102] The reaction temperature is not specifically restricted; it mayrange from −100° C. to the boiling point of the solvent. Preferredreaction temperatures are within the range from −80° C. to 40° C. Thereaction time is usually 0.1 to 1000 hours.

[0103] The above-mentioned reaction gives rise to the organotitaniumcompound represented by the above-mentioned formula (12). This compoundis unstable out of the reaction system. Therefore, it is not isolated assuch. Instead, the reaction system is given an electrophilic reagent tobring about addition reaction at the titanium bonding position, and theresulting addition product is isolated afterwards.

[0104] It is presumed that the organotitanium compound represented bythe formula (12) is formed by the following reaction mechanism. Thereaction mechanism is identical with that mentioned above, except thattwo molecules of the acetylene compounds represented by the formulas (4)and (5) are replaced by the diyne compound represented by the formula(11). The reaction product has such a structure that thetitanacyclopentadiene intermediate is connected to the acetylenecompound as the third component. This determines the orientation of thecyclic addition and gives rise to a single organotitanium compound.

[0105] A mention is made below of the process for producing theorganotitanium compound represented by the formulas (14) above.

[0106] The acetylene compound represented by the formula (1) is reactedwith two molecules of the acetylene compound represented by the formula(13) above in the presence of the titanium compound represented by theformula (2) above and the Grignard reagent represented by the formula(3) above. In this way it is possible to produce the organotitaniumcompound represented by the formula (14) above.

[0107] The molar amount of the titanium compound used in this reactionis 0.01-5 times, preferably 0.5-2 times, the amount of the acetylenecompound (as the substrate) represented by the formula (1). The molaramount of the Grignard reagent should be 1-10 times the amount of thetitanium compound used. The amount should be limited to 1.5-2.5 times inorder to avoid side reactions with the substrate.

[0108] The reaction may be carried out by adding the reactants in anyorder. One procedure involves mixing the titanium compound and theGrignard reagent and then adding to the mixture the acetylene compound(as the substrate) represented by the formula (1). Another procedureinvolves adding the titanium compound to the acetylene compoundrepresented by the formula (1), and then adding the Grignard reagent.Either procedure will do.

[0109] The molar amount of the acetylene compound represented by theformula (13) is 1-4 times, preferably 1.6-3 times, the amount of theacetylene compound represented by the formula (1).

[0110] The solvent used in the reaction is not specifically restrictedso long as it is not involved in the reaction. It includes those whichhave been listed above.

[0111] The reaction temperature is not specifically restricted; it mayrange from −100° C. to the boiling point of the solvent. Preferredreaction temperatures are within the range from −80° C. to 40° C. Thereaction time is usually 0.1 to 1000 hours.

[0112] The above-mentioned reaction gives rise to the organotitaniumcompound represented by the above-mentioned formula (14). This compoundis unstable out of the reaction system. Therefore, it is not isolated assuch. Instead, the reaction system is given an electrophilic reagent tobring about addition reaction at the titanium bonding position, and theresulting addition product is isolated afterwards.

[0113] It is presumed that the organotitanium compound represented bythe formula (14) is formed by the following reaction mechanism.

[0114] The titanium compound and the Grignard reagent give rise to adivalent titanium complex, which reacts with two molecules of thecompounds having a triple bond to give a titanacyclopentadieneintermediate. This intermediate reacts with one molecule of the compoundrepresented by the formula (13) for cyclic addition reaction. Thisaddition reaction brings about transfer of titanium-carbon bond andeliminates the leaving group, thereby giving rise to the organotitaniumcompound represented by the formula (14).

[0115] (B) Process For Addition Reaction

[0116] According to the present invention, the process for additionreaction consists of adding to the organotitanium compound obtained bythe above-mentioned process a compound having an electrophilicfunctional group or an electrophilic reagent, and performing additionreaction on the organotitanium compound.

[0117] The electrophilic functional group is not specifically restrictedso long as it reacts with the organotitanium compound of the presentinvention. It is preferably aldehyde group, ketone group, imino group,hydrazone group, aliphatic double bond, aliphatic triple bond, acylgroup, ester group, or carbonate group. The compound having anelectrophilic functional group includes, for example, aldehyde compound,ketone compound, imine compound, hydrazone compound, olefin compound,acetylene compound, acyl compound, ester compound, α,β-unsaturatedcarbonyl compound, and carbonate ester compound.

[0118] The aldehyde compound is not specifically restricted. Itincludes, for example, C₁₋₁₀ alkyl aldehyde, C₄₋₆ cycloalkyl aldehyde,C₃₋₁₄ cycloalkenyl aldehyde, benzaldehyde, o-halogenobenzaldehyde,m-halogenobenzaldehyde, p-halogeno-benzaldehyde, C₁₋₁₀ alkylester-substituted phenyl aldehyde, o-halogenosuccin aldehyde,m-halogenosuccin aldehyde, p-halogenosuccin aldehyde, furylaldehyde, andthiophen aldehyde.

[0119] The ketone compound includes, for example, C₃₋₂₀ alkyl ketone,C₄₋₃₀ alkyl ester-substituted alkyl ketone, C₃₋₁₀ cycloalkyl ketone,acetophenone, tetralone, decalone, furyl ketone, and thiophenoketone.The imine compound includes, for example, the reaction product of theabove-mentioned aldehyde compound with C₁₋₁₀ alkylamine, aniline, orbenzylamine.

[0120] The hydrazone compound includes, for example, the reactionproduct of the above-mentioned ketone compound with C₁₋₁₀ alkylhydrazine.

[0121] The olefin compound includes, for example, allyl alcoholderivatives which may have a substituent group. The allyl alcoholderivative includes, for example, C₄₋₁₃ allyl alcohol alkyl ester andC₄₋₁₃ allyl alcohol alkyl carbamate.

[0122] The allyl alcohol derivative may have a substituent group such asC₁₋₂₀ alkyl group, phenyl group, o-halogeno-phenyl group,m-halogenophenyl group, and p-halogenophenyl group.

[0123] The acetylene compound includes, for example, propargyl alcoholderivative which may have a substituent group and propargyl halide whichmay have a substituent group. The propargyl alcohol derivative includes,for example, C₄₋₁₃ propargyl alcohol alkyl ester, C₄₋₁₃ propargylalcohol alkyl carbamate, C₄₋₁₃ propargyl alcohol alkyl ether, C₄₋₁₃propargyl alcohol alkylsulfonic ester, propargylalcohol-o-hydroxyphenylsulfonic ester, propargylalcohol-m-hydroxyphenylsulfonic ester, propargylalcohol-p-hydroxy-phenylsulfonic ester, and C₄₋₁₃ propargyl alcoholalkyl phosphoric ester.

[0124] The propargyl halide includes, for example, propargyl chlorideand propargyl bromide.

[0125] These propargyl alcohol derivatives and propargyl halides mayhave a substituent group such as C₁₋₂₀ alkyl group, phenyl group,o-halogenophenyl group, m-halogenophenyl group, p-halogenophenyl group,and trialkylsilyl group.

[0126] The electrophilic reagent is not specifically restricted so longas it reacts with the organotitanium compound of the present invention.It is preferably water, heavy water, chlorine, bromine, iodine,N-bromosuccinimide, oxygen, carbon dioxide gas, or carbon monoxide.

[0127] To be concrete, the process consists of adding to theorganotitanium compound (prepared as mentioned above) the compoundhaving an electrophilic functional group or the electrophilic reagent(which are collectively referred to as an electrophilic compoundhereinafter), thereby causing addition reaction with the electrophiliccompound to take place at the titanium bonding position.

[0128] The molar amount of the electrophilic compound should be 1-10times, preferably 1-5 times, particularly 1-2 times, the amount of theorganotitanium compound.

[0129] The reaction may be carried out by adding the electrophiliccompound in any order. One procedure involves adding the electrophiliccompound directly to the reaction system in which the organotitaniumcompound has been prepared. Another procedure involves adding a solutionof the organotitanium compound to a solution in which the electrophiliccompound has been dissolved. Either procedure will do.

[0130] The solvent used in the reaction is not specifically restrictedso long as it is not involved in the reaction. It includes those whichhave been used for the production of the organotitanium compound.

[0131] The reaction temperature is not specifically restricted; it mayrange from −100° C. to the boiling point of the solvent. Preferredreaction temperatures are within the range from −80° C. to 40° C. Thereaction time is usually 0.1 to 1000 hours.

[0132] After the reaction is complete, the addition reaction product isextracted with an adequate solvent, and there is obtained a crudeproduct upon condensation under reduced pressure. If necessary, thecrude product is purified in the usual way by distillation,recrystallization, silica gel column chromatography, or the like. Inthis way it is possible to isolate the desired product in pure form.

EXAMPLES

[0133] The invention will be described in more detail with reference tothe following examples, which are not intended to restrict the scopethereof.

[0134] In the structural formulas given below, Me denotes methyl group,Et denotes ethyl group, Bn denotes benzyl group, t-Bu denotes t-butylgroup, Ph denotes phenyl group, Tol denotes p-tolyl group, and TBSdenotes t-butyldimethylsilyl group.

Example 1

[0135]3-(t-butoxycarbonyl)-4-hexylphenyl p-tolylsulfone

[0136] To a diethyl ether solution (7 mL) containing t-butyl 2-nonynoate(100 mg, 0.475 mmol) and tetra-i-propoxytitanium (0.175 mL, 0.594 mmol)was added i-propylmagnesium chloride (1.48 M diethyl ether solution,0.900 mL, 1.33 mmol) at −78° C. under an argon stream. There wasobtained a homogenous yellowish solution. The solution was slowly heatedto −50° C. over 30 minutes. The solution turned into reddish. Thesolution was kept stirred for 5 hours at −50° C. The solution kept at−50° C. was given a diethyl ether solution (2 mL) containing powderyp-toluenesulfonyl-acetylene (171 mg, 0.951 mmol). Stirring was continuedfor 1 hour.

[0137] The reaction solution at room temperature was stirred for 3 hoursand then given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether.

[0138] The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was analyzed indetail by ¹H NMR. It was found to contain no other isomers. The crudeproduct was purified by silica gel column chromatography (n-hexane-ethylacetate). There was obtained 3-(t-butoxy-carbonyl)-4-hexylphenylp-tolylsulfone (98 mg, 50%) in the form of colorless oily substance.

[0139]¹H NMR: δ 0.84 (t, J=6.6 Hz, 3H, Me), 1.12-1.40 (m, 6H, alkyl H),1.45-1.65 (m, 2H, alkyl H), 1.58 (s, 9H, C(CH₃)₃), 2.37 (s, 3H, PhMe),2.90 (t, J=7.8 Hz, 2H, PhCH₂), 7.28 (d, J=8.4 Hz, 2H, Ph-H), 7.32 (d,J=8.1 Hz, 1H, Ph-H), 7.81 (d, J=8.4 Hz, 2H, Ph-H), 7.86 (dd, J=2.1, 8.1Hz, 1H, Ph-H), 8.23 (d, J=2.1 Hz, 1H, Ph-H).

[0140] The structure was confirmed (identified) by the fact that a 12%increase in NOE (nuclear Overhauser effect) due to proton at δ 2.90 ppm(PhCH₂) was observed in the peak at δ 7.32 ppm (Ph-H).

[0141]¹³C NMR: δ 13.84, 21.37, 22.35, 27.95 (C(CH₃)₃), 29.18, 31.39,31.49, 34.21, 82.30 (CO₂C), 127.74 (o- or m-Ph), 129.26 (Ph), 129.47(Ph), 129.98 (o- or m-Ph), 131.73 (Ph), 133.18 (Ph), 138.53 (Ph), 139.48(Ph), 144.30 (Ph), 149.06 (Ph), 165.05 (C═O).

[0142] IR (neat): 3070 (Ph), 2960, 2927, 2860, 1715 (C═O), 1597, 1457,1369 (S═O), 1256, 1156 (S═O), 914, 846, 813 cm⁻¹.

[0143] Elemental analysis: calculated (C₂₄H₃₂O₄S): C, 69.20%; H, 7.74%.found: C, 69.16%; H, 7.62%.

Example 2

[0144]3,4-dibutylphenyl p-tolylsulfone

[0145] To a diethyl ether solution (1.5 mL) containing 5-decyne (0.020mL, 0.111 mmol) and tetra-i-propoxytitanium (0.041 mL, 0.139 mmol) wasadded i-propylmagnesium chloride (1.63 M diethyl ether solution, 0.192mL, 0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution (kept at −50° C.) wasgiven a diethyl ether solution (1 mL) containing powderyp-toluenesulfonyl-acetylene (40 mg, 0.223 mmol). Stirring was continuedfor 1 hour.

[0146] The reaction solution at room temperature was stirred for 3 hoursand then given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether.

[0147] The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was analyzed indetail by ¹H NMR. It was found that it contained no other isomers. Thecrude product was purified by silica gel column chromatography(n-hexane-ethyl acetate). There was obtained 3,4-dibutylphenylp-tolylsulfone (25 mg, 65%) in the form of colorless oily substance.

[0148]¹H NMR: δ 0.92 (t, J=7.5 Hz, 3H, Me), 0.94 (t, J=7.5 Hz, 3H, Me),1.38 (sextet, J=7.5 Hz, 4H, alkyl H), 1.52 (quintet, J=7.5 Hz, 4H, alkylH), 2.39 (s, 3H, PhMe), 2.61 (t, J=7.5 Hz, 2H, PhMe), 2.62 (t, J=7.5 Hz,2H, PhCH₂), 7.23 (d, J=8.1 Hz, 1H, Ph-H), 7.28 (d, J=8.4 Hz, 2H, Ph-H),7.63 (dd, J=2.1, 8.1 Hz, 1H, Ph-H), 7.70 (d, J =2.1 Hz, 1H, Ph-H), 7.82(d, J=8.4 Hz, 2H, Ph-H).

[0149]¹³C NMR: δ 13.78 (2 peaks), 21.42, 22.58 (2 peaks), 32.21, 32.26,32.87, 32.89, 124.97 (Ph), 127.63 (o- or m-Ph), 127.96 (Ph), 129.87 (o-or m-Ph), 130.01 (Ph), 139.05 (Ph), 139.32 (Ph), 142.09 (Ph), 143.86(Ph), 146.64 (Ph).

[0150] IR (neat): 3060 (Ph), 3020 (Ph), 2957, 2929, 2870, 1597, 1465,1402, 1379, 1320 (S═O), 1301, 1179, 1154 (S═O), 1107, 1085, 911, 812,733, 708, 683 cm¹.

[0151] Elemental analysis: calculated (C₂₁H₂₈O₂S): C, 73.21%; H, 8.19%.found: C, 73.04%; H, 8.07%.

Example 3

[0152] 5-(t-butoxycarbonyl)-2-deuterio-4-hexylphenyl p-tolylsulfone.

[0153] The same procedure as in Example 1 was repeated except that heavywater was added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained 5-(t-butoxycarbonyl)-2-deuterio-4-hexylphenylp-tolylsulfone.

[0154]¹H NMR: δ 0.84 (t, J=6.6 Hz, 3H, Me), 1.12-1.40 (m, 6H, alkyl H),1.45-1.65 (m, 2H, alkyl H), 1.58 (s, 9H, C(CH₃)₃), 2.37 (s, 3H, PhMe),2.90 (t, J=7.8 Hz, 2H, PhCH₂), 7.28 (d, J=8.4 Hz, 2H, Ph-H), 7.32 (s,1H, Ph-H), 7.81 (d, J=8.4 Hz, 2H, Ph-H), 8.23 (s, 1H, Ph-H).

[0155] An introduction of 78% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.86 (Ph-H) of3-(t-butoxycarbonyl)-4-hexylphenyl p-tolylsulfone.

Example 4

[0156] 4,5-dibutyl-2-deuteriophenyl p-tolylsulfone

[0157] The same procedure as in Example 2 was repeated except that heavywater was added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained 4,5-dibutyl-2-deuteriophenyl p-tolylsulfone.

[0158]¹H NMR: δ 0.92 (t, J=7.5 Hz, 3H, Me), 0.94 (t, J=7.5 Hz, 3H, Me),1.38 (sextet, J=7.5 Hz, 4H, alkyl H), 1.52 (quintet, J=7.5 Hz, 4H, alkylH), 2.39 (s, 3H, PhMe), 2.61 (t, J=7.5 Hz, 2H, PhCH₂), 2.62 (t, J=7.5Hz, 2H, PhCH₂), 7.23 (s, 1H, Ph-H), 7.28 (d, J=8.4 Hz, 2H, Ph-H), 7.70(s, 1H, Ph-H), 7.82 (d, J=8.4 Hz, 2H, Ph-H).

[0159] An introduction of 80% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.63 (Ph-H) of3,4-dibutylphenyl p-tolylsulfone.

Example 5

[0160] t-butyl 2,4-dihexylbenzoate

[0161] To a diethyl ether solution (1.5 mL) containing t-butyl2-nonynoate (20 mg, 0.095 mmol) and tetra-i-propoxy-titanium (0.035 mL,0.119 mmol) was added i-propylmagnesium chloride (1.63 M diethyl ethersolution, 0.163 mL, 0.266 mmol) at −78° C. under an argon stream. Therewas obtained a homogenous yellowish solution. The solution was slowlyheated to −50° C. over 30 minutes. The solution turned into reddish. Thesolution was kept stirred for 5 hours at −50° C. The solution (kept at−50° C.) was given 1-octyne (0.011 mL, 0.076 mmol), and the solution wasstirred for 3 hours. The solution was given a diethyl ether solution (1mL) containing powdery p-toluenesulfonylacetylene (21 mg, 0.114 mmol).The reaction solution was heated to room temperature.

[0162] The reaction solution (at room temperature) was stirred for 3hours and then given hydrochloric acid (1 mol/L) to suspend thereaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-diethyl ether).There was obtained t-butyl 2,4-dihexylbenzoate (15 mg, 57%) in the formof colorless oily substance.

[0163]¹H NMR: δ 0.87, (t, J=7.5 Hz, 6H, Me), 1.20-1.42 (m, 16H, alkylH), 1.58 (s, 9H, C(CH₃)₃), 2.58 (t, J=7.8 Hz, 2H, PhCH₂), 2.89 (t, J=7.8Hz, 2H, PhCH₂), 7.00 (s, 1H, Ph-H), 7.01 (d, J=8.4 Hz, 1H, Ph-H), 7.67(d, J=8.4 Hz, 1H, Ph-H).

[0164] The structure was confirmed (identified) by the fact that a 5%increase in NOE due to irradiate proton at δ 2.58 ppm (PhCH₂) wasobserved in both the peak at δ 7.00 ppm (Ph-H) and the peak at δ 7.01ppm (Ph-H) and the fact that a 9% increase in NOE due to proton at δ2.89 ppm (PhCH₂) was observed in the peak at δ 7.00 ppm (Ph-H).

[0165]¹³C NMR: δ 13.96 (2 peaks), 22.49, 22.53, 28.15 (C(CH₃)₃), 28.87,29.38, 31.08, 31.60, 31.74, 31.89, 34.44, 35.71, 80.76 (CO₂C), 125.73(Ph), 129.25 (Ph), 130.54 (Ph), 130.96 (Ph), 143.81 (Ph), 146.49 (Ph),167.80 (C═O),

[0166] IR (neat): 3010 (Ph), 2957, 2928, 2857, 1716 (C═O), 1609, 1458,1366, 1275, 1258, 1180, 1142, 1100, 1071, 1100, 1070 cm⁻¹.

[0167] Elemental analysis: calculated (C₂₃H₃₈O₂): C, 79.71%; H, 11.05%.found: C, 79.57%; H, 10.84%.

[0168] The synthesized sample was found identical with the referencematerial of t-butyl 2,4-dihexylbenzoate which was synthesized separatelyfrom commercial 4-bromoisophthalic acid in the following manner.

Example 6

[0169] t-butyl 2,4-dihexylbenzoate

[0170] The same procedure as in Example 5 was repeated except thatp-toluenesulfonylacetylene was replaced by p-toluene-sulfinylacetylene.There was obtained t-butyl 2,4-dihexyl-benzoate in a 17% yield.

Example 7

[0171] t-butyl 2-deuterio-4,6-dihexylbenzoate

[0172] The same procedure as in Example 5 was repeated except that heavywater was added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained t-butyl 2-deuterio-4, 6-dihexylbenzoate.

[0173]¹H NMR: δ 0.87 (t, J=7.5 Hz, 6H, Me), 1.20-1.42 (m, 16H, alkyl H),1.58 (s, 9H, C(CH₃)₃), 2.58 (t, J=7.8 Hz, 2H, PhCH₂), 2.89 (t, J=7.8 Hz,2H, PhCH₂), 7.01 (s, 2H, Ph-H).

[0174] An introduction of 98% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.67 (Ph-H) oft-butyl 2,4-dihexylbenzoate.

Example 8

[0175] t-butyl 2,4-dihexyl-6-iodobenzoate

[0176] To a diethyl ether solution (1.5 mL) containing t-butyl2-nonynoate (20 mg, 0.095 mmol) and tetra-i-propoxy-titanium (0.035 mL,0.119 mmol) was added i-propylmagnesium chloride (1.63 M diethyl ethersolution, 0.163 mL, 0.266 mmol) at −78° C. under an argon stream. Therewas obtained a homogenous yellowish solution. The solution was slowlyheated to −50° C. over 30 minutes. The solution turned into reddish. Thesolution was kept stirred for 5 hours at −50° C. The solution kept at−50° C. was given 1-octyne (0.011 mL, 0.076 mmol), and the solution wasstirred for 3 hours. The solution was given a diethyl ether solution (1mL) containing powdery p-toluenesulfonylacetylene (21 mg, 0.114 mmol).The reaction solution was heated to room temperature.

[0177] The reaction solution was stirred at room temperature for 3 hoursand then given a tetrahydrofuran solution (1 mL) containing iodine (72mg, 0.285 mmol). The solution was stirred for 1 hour and then givenhydrochloric acid (1 mol/L) to suspend the reaction. The reactionproduct was extracted with diethyl ether. The organic layer was washedwith an aqueous solution of sodium bicarbonate and sodium thiosulfateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-diethyl ether).There was obtained t-butyl 2,4-dihexyl-6-iodobenzoate (20 mg, 56%) inthe form of colorless oily substance.

[0178]¹H NMR: δ 0.80-0.95 (m, 6H, Me), 1.12-1.45 (m, 16H, alkyl H), 1.62(s, 9H, C(CH₃)₃), 2.50 (t, J=7.8 Hz, 2H, PhCH₂), 2.57 (t, J=7.8 Hz, 2H,PhCH₂), 6.95 (d, J=1.5 Hz, 1H, Ph-H), 7.46 (d, J=1.5 Hz, 1H, Ph-H).

[0179]¹³C NMR: δ 13.93 (2 peaks), 22.45 (2 peaks), 28.01 (C(CH₃)₃),28.76, 29.22, 31.01, 31.37, 31.53, 31.57, 34.18, 35.14, 82,71 (CO₂C),91.96 (Ph), 129.22 (Ph), 136.47 (Ph), 138.16 (Ph), 140.91 (Ph), 145.46(Ph), 168.52 (C═O).

[0180] IR (neat): 3010 (Ph), 2960, 2927, 2857, 1725 (C═O), 1600, 1546,1458, 1391, 1367, 1285, 1260, 1146, 1101, 1070, 847 cm⁻¹.

Example 9

[0181] 5,7-dihexyl-3-phenylphthalide

[0182] To a diethyl ether solution (1.5 mL) containing t-butyl2-nonynoate (30 mg, 0.143 mmol) and tetra-i-propoxy-titanium (0.053 mL,0.178 mmol) was added i-propylmagnesium chloride (1.35 M diethyl ethersolution, 0.296 mL, 0.399 mmol) at −78° C. under an argon stream. Therewas obtained a homogenous yellowish solution. The solution was slowlyheated to −50° C. over 30 minutes. The solution turned into reddish. Thesolution was kept stirred for 5 hours at −50° C. The solution kept at−50° C. was given 1-octyne (0.017 mL, 0.114 mmol), and the solution wasstirred for 3 hours. The solution was given a diethyl ether solution (1mL) containing powdery p-toluenesulfonylacetylene (31 mg, 0.171 mmol).The reaction solution was heated to room temperature. The reactionsolution was stirred at room temperature for 3 hours and then cooled to−50° C. The solution was given benzaldehyde (0.899 M, diethyl ethersolution, 0.190 mL, 0.171 mmol). The solution was stirred at −50° C. for2 hours and then heated to room temperature. Stirring was continued atroom temperature for 5 hours.

[0183] The solution was given hydrochloric acid (1 mol/L) to suspend thereaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-diethyl ether).There was obtained 5,7-dihexyl-3-phenylphthalide (21 mg, 49%) in theform of colorless oily substance.

[0184]¹H NMR: δ 0.80-0.95 (m, 6H, Me), 1.20-1.50 (m, 12H, alkyl H),1.50-1.76 (m, 4H, alkyl H), 2.62 (t, J=7.8 Hz, 2H, PhCH₂), 3.06 (dt,J=2.1, 7.8 Hz, 1H, PhCH₂), 3.13 (dt, J=2.1, 7.8 H, 1H, PhCH₂), 6.27 (s,1H, C0₂CH), 6.90 (s, 1H, Ph-H), 7.11 (s, 1H, Ph-H), 7.25-7.31 (m, 2H,Ph-H), 7.34-7.42 (m, 3H, Ph-H).

[0185] The structure was confirmed (identified) by the fact that a 9%increase in NOE due to irradiate proton at δ 2.62 ppm (PhCH₂) wasobserved in both the peak at δ 6.90 ppm (Ph-H) and the peak at δ 7.11ppm (Ph-H) and the fact that a 9% increase in NOE due to irradiateproton at δ 3.06 ppm (PhCH₂) and proton at δ 3.13 ppm (PhCH₂) wasobserved in the peak at δ 7.00 ppm (Ph-H).

[0186]¹³C NMR: δ 13.88, 13.95, 22.41, 22.49, 28.81, 29.04, 30.89, 30.92,31.06, 31.47, 31.59, 36.18, 81.53 (CO₂C), 119.95 (Ph), 120.32 (Ph),127.10 (o- or m-Ph), 128.93 (m- or o-Ph), 129.10 (Ph), 130.52 (Ph),137.29 (Ph), 144.63 (Ph), 150.32 (Ph), 151.03 (Ph), 170.54 (C═O).

[0187] IR (neat): 3070 (Ph), 3038 (Ph), 2960, 2860, 1761 (C═O), 1610,1458, 1301, 1204, 1056, 698 cm⁻¹.

Example 10

[0188] t-butyl 2-hexyl-4-(trimethylsilyl)benzoate

[0189] The same procedure as in Example 5 was repeated except that1-octyne was replaced by trimethylsilylacetylene. There was obtainedt-butyl 2-hexyl-4-(trimethylsilyl)-benzoate in a 46% yield.

[0190]¹H NMR: δ 0.27 (s, 9H, SiMe₃), 0.88, (t, J=7.5 Hz, 3H, Me),1.15-1.45 (m, 8H, alkyl H), 1.59 (s, 9H, C(CH₃)₃), 2.90 (t, J=7.8 Hz,2H, PhCH₂), 7.33 (s, 1H, Ph-H), 7.36 (d, J=7.5 Hz, 1H, Ph-H), 7.69 (d,J=7.5 Hz, 1H, Ph-H).

[0191]¹³C NMR: δ −1.43 (SiMe₃), 13.96, 22.55, 28.12 (C(CH₃)₃), 29.42,31.71, 32.02, 34.43, 81.05 (CO₂C), 129.13 (Ph), 130.61 (Ph), 132.43(Ph), 135.80 (Ph), 142.20 (Ph), 144.37 (Ph), 167.99 (C═O).

[0192] IR (neat): 3005 (Ph), 2957, 2925, 2860, 1717 (C═O), 1458, 1367,1250 (SiMe₃), 1150, 840 cm⁻¹. Elemental analysis: calculated(C₂₀H₃₄O₂Si): C, 71.80%; H, 10.24%. found: C, 71.64%; H, 10.53%.

Example 11

[0193] t-butyl 2-deuterio-6-hexyl-4-(trimethylsilyl)benzoate

[0194] The same procedure as in Example 10 was repeated except thatheavy water was added for reaction before the addition of hydrochloricacid (1 mol/L). There was obtained t-butyl2-deuterio-6-hexyl-4-(trimethylsilyl)benzoate.

[0195]¹H NMR: δ 0.27 (s, 9H, SiMe₃), 0.88 (t, J=7.5 Hz, 3H, Me),1.15-1.45 (m, 8H, alkyl H), 1.59 (s, 9H, C(CH₃)₃), 2.90 (t, J=7.8 Hz,2H, PhCH₂), 7.33 (s, 1H, Ph-H), 7.36 (s, 1H, Ph-H).

[0196] An introduction of 94% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.69 (Ph-H) oft-butyl 2-hexyl-4-trimethylsilyl)benzoate.

Example 12

[0197] 4-[2-(benzyloxy)ethyl]-1,2-dibutylbenzene

[0198] To a diethyl ether solution (1.5 mL) containing 5-decyne (0.02mL, 0.111 mmol) and tetra-i-propoxytitanium (0.041 mL, 0.139 mmol) wasadded i-propyl-magnesium chloride (1.63 M diethyl ether solution, 0.192mL, 0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution kept at −50° C. wasgiven a diethyl ether solution (1 mL) containing 4-benzyloxy-1-butyne(14 mg, 0.089 mmol) and then stirred for 1 hour. The solution was givena diethyl ether solution (1 mL) containing powderyp-toluenesulfonylacetylene (22 mg, 0.122 mmol). The reaction solutionwas heated to room temperature.

[0199] The reaction solution at room temperature was stirred for 3 hoursand then given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether. The organic layer waswashed with an aqueous solution of sodium bicarbonate and then driedwith anhydrous sodium sulfate. The solvent was distilled away underreduced pressure. There was obtained a crude product in the form of oilysubstance. The crude product was analyzed in detail by ¹H NMR. It wasfound to contain no other isomers. The crude product was purified bysilica gel column chromatography (n-hexane-diethyl ether). There wasobtained 4-[2-(benzyloxy)ethyl]-1,2-dibutylbenzene (17 mg, 57%) in theform of colorless oily substance.

[0200]¹H NMR: δ 0.95 (t, J=7.5 Hz, 6H, Me), 1.40 (sextet, J=7.5 Hz, 4H,alkyl H), 1.52 (quintet, J=7.5 Hz, 4H, alkyl H), 2.58 (t, J=7.5 Hz, 4H,PhCH₂), 2.89 (t, J=7.5 Hz, 2H, PhCH₂), 3.68 (t, J=7.5 Hz, 2H, CH₂OBn),4.54 (s, 2H, PhCH₂O), 6.98 (d, J=7.5 Hz, 1H, Ph-H), 7.00 (s, 1H, Ph-H),7.06 (d, J=7.5 Hz, 1H, Ph-H), 7.25-7.40 (m, 5H, Ph-H).

[0201]¹³C NMR: δ 13.91 (2 peaks), 22.73, 22.80, 31.93, 32.34, 33.46,33.49, 35.89, 71.48 (O—C), 72.91 (O—C), 126.29 (Ph), 127.57 (Ph), 127.71(o- or m-Ph), 128.41 (m- or o-Ph), 129.19 (Ph), 129.85 (Ph), 136.12(Ph), 138.47 (Ph), 138.60 (Ph), 140.60 (Ph).

[0202] IR (neat): 3090 (Ph), 3070 (Ph), 3035 (Ph), 3000 (Ph), 2955 (Ph),2928, 2859, 1497, 1456, 1362, 1205, 1102, 1029, 822, 734, 696 cm⁻¹.

[0203] Elemental analysis: calculated (C₂₃H₃₂O): C, 85.13%; H, 9.94%.found: C, 85.38%; H, 10.03%.

Example 13

[0204] A 72:28 mixture of1-[2-(benzyloxy)ethyl]-4,5-dibutyl-2-iodobenzene and5-[2-(benzyloxy)ethyl]-1,2-dibutyl-3-iodobenzene.

[0205] The same procedure as in Example 12 was repeated except thatiodine was added for reaction before the addition of hydrochloric acid(1 mol/L). There was obtained a 72:28 mixture of1-[2-(benzyloxy)ethyl]-4,5-dibutyl-2-iodobenzene and5-[2-(benzyloxy)ethyl]-1,2-dibutyl-3-iodobenzene in a 39% yield.

[0206] 1-[2-(benzyloxy)ethyl]-4,5-dibutyl-2-iodobenzene

[0207] (Analyzed from a 72:28 mixture of position isomers.)

[0208]¹H NMR: δ 0.80-1.04 (m, 6H, Me), 1.20-1.60 (m, 8H, alkyl H), 2.51(t, J=7.7 Hz, 4H, PhCH₂), 3.00 (t, J=7.5 Hz, 2H, PhCH₂), 3.66 (t, J=7.5Hz, 2H, CH₂OBn), 4.55 (s, 2H, PhCH₂O), 7.03 (s, 1H, Ph-H), 7.25-7.40 (m,5H, Ph-H), 7.56 (s, 1H, Ph-H).

[0209] The structure was confirmed (identified) by the fact that a 9%increase and a 13% increase in NOE due to irradiate proton at δ 2.51 ppm(PhCH₂) were observed respectively in the peaks at δ 7.03 ppm (Ph-H) andδ 7.56 ppm (Ph-H) and the fact that a 14% increase in NOE due toirradiate proton at δ 3.00 ppm (PhCH₂) was observed in the peak at δ7.03 ppm (Ph-H).

[0210] IR (neat): 3090 (Ph), 3060 (Ph), 3035 (Ph), 2955, 2928, 2859,1456, 1380, 1362, 1205, 1102, 1030, 733, 696 cm⁻¹.

[0211] 5-[2-(benzyloxy)ethyl]-1,2-dibutyl-3-iodobenzene

[0212]¹H NMR: (characteristic peaks only) δ 2.80 (t, J=7.5 Hz, 2H,PhCH₂), 3.65 (t, J=7.5 Hz, 2H, CH₂OBn), 4.52 (s, 2H, PhCH₂O), 6.96 (s,1H, Ph-H), 7.56 (s, 1H, Ph-H).

Example 14

[0213]4-[2-((t-butyl)dimethylsiloxy)ethyl]-2-hexyl-1-(trimethyl-silyl)benzene

[0214] To a diethyl ether solution (4.5 mL) containing1-trimethylsilyl-l-octyne (60 mg, 0.329 mmol) andtetra-i-propoxytitanium (0.121 mL, 0.411 mmol) was addedi-propyl-magnesium chloride (1.46 M diethyl ether solution, 0.630 mL,0.921 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution kept at −50° C. wasgiven a diethyl ether solution (1 mL) containing4-[(t-butyl)dimethylsiloxy]-1-butyne (48 mg, 0.263 mmol) and thenstirred for 1 hour. The solution was given a diethyl ether solution (1mL) containing powdery p-toluenesulfonylacetylene (71 mg, 0.395 mmol).The reaction solution was heated to room temperature.

[0215] The reaction solution (at room temperature) was stirred for 3hours and then given hydrochloric acid (1 mol/L) to suspend thereaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-diethyl ether).There was obtained4-[2-((t-butyl)dimethylsiloxy)ethyl]-2-hexyl-1-(trimethylsilyl)benzene(52 mg, 50%) in the form of colorless oily substance.

[0216]¹H NMR: δ 0.02 (s, 6H, t-BuSiMe₂), 0.31 (s, 9H, SiMe₃), 0.80-0.95(m, 3H, Me,), 0.89 (s, 9H, C(CH₃)₃), 1.20-1.50 (m, 6H, alkyl H),1.50-1.68 (m, 2H, alkyl H), 2.67 (t, J=8.1 Hz, 2H, PhCH₂), 2.80 (t,J=7.2 Hz, 2H, PhCH₂), 3.81 (t, J=7.2 Hz, 2H, CH₂OTBS), 7.02 (d, J=7.5Hz, 1H, Ph-H), 7.06 (s, 1H, Ph-H), 7.38 (d, J=7.5 Hz, 1H, Ph-H).

[0217]¹³C NMR: δ −5.22 (t-BuSiMe₂), 0.37 (SiMe₃), 13.96, 18.24(C(CH₃)₃), 22.53, 25.85 (C(CH₃)₃), 29.60, 31.74, 32.59, 36.30, 39.46,64.50 (O—C), 125.82 (Ph), 129.57 (Ph), 134.64 (Ph), 135.34 (Ph), 140.12(Ph), 148.93 (Ph).

[0218] IR (neat): 3045 (Ph), 2960, 2928, 2857, 1604, 1470, 1250 (C—Si),1098, 837, 775 cm⁻¹.

[0219] Elemental analysis: calculated (C₂₃H₄₄OSi₂): C, 70.33%; H,11.29%. found: C, 70.54%; H, 11.58%.

Example 15

[0220] A 74:26 mixture of1-[2-((t-butyl)dimethylsiloxy)-ethyl]-5-hexyl-2-iodo-4-(trimethylsilyl)benzeneand5-[2-((t-butyl)dimethylsiloxy)ethyl]-1-hexyl-3-iodo-2-(trimethylsilyl)benzene

[0221] The same procedure as in Example 14 was repeated except thatiodine was added for reaction before the addition of hydrochloric acid(1 mol/L). There was obtained a 74:26 mixture of1-[2-((t-butyl)dimethylsiloxy)ethyl]-5-hexyl-2-iodo-4-(trimethylsilyl)benzeneand5-[2-((t-butyl)dimethylsiloxy)ethyl]-1-hexyl-3-iodo-2-(trimethylsilyl)benzenein a 37% yield.

[0222]1-[2-((t-butyl)dimethylsiloxy)ethyl]-5-hexyl-2-iodo-4-(trimethylsilyl)benzene

[0223] (Analyzed from a 74:26 mixture of position isomers.)

[0224]¹H NMR: δ 0.01 (s, 6H, t-BuSiMe₂), 0.29 (s, 9H, SiMe₃), 0.80-0.95(m, 3H, Me), 0.87 (s, 9H, C(CH₃)₃), 1.20-1.50 (m, 6H, alkyl H),1.60-1.72 (m, 2H, alkyl H), 2.60 (t, J=8.1 Hz, 2H, PhCH₂), 2.91 (t,J=7.2 Hz, 2H PhCH₂), 3.79 (t, J=7.2 Hz, 2H CH₂OTBS), 7.09, (s, 1H,Ph-H), 7.80 (s, 1H, Ph-H).

[0225] The structure was confirmed (identified) by the fact that a 12%increase in NOE due to irradiate proton at δ 0.01 ppm (SiMe₃) wasobserved in the peak at δ 7.80 ppm (Ph-H).

[0226] IR (neat): 3038 (Ph), 2954, 2927, 2856, 1591, 1524, 1463, 1379,1360, 1250 (Si—C), 1098, 1006, 909, 837, 776, 734 cm⁻¹.

[0227]5-[2-((t-butyl)dimethylsiloxy)ethyl]-1-hexyl-3-iodo-2-(trimethylsilyl)benzene

[0228]¹H NMR: (characteristic peaks only) δ 0.01 (s, 6H, t-BuSiMe₂),0.53 (s, 9H, SiMe₃), 2.66 (t, J=8.1 Hz, 2H, PhCH₂), 2.67 (t, J=6.6 Hz,2H, PhCH₂), 3.77 (t, J=6.6 Hz, 2H, CH₂OTBS), 6.97 (d, J=1.5 Hz, 1H,Ph-H), 7.68 (d, J=1.5 Hz, 1H, Ph-H).

Example 16

[0229] 2,3-bis(cyclohexyloxy)-1,4-bis(trimethylsilyl)benzene

[0230] To a diethyl ether solution (1.5 mL) containingcyclohexyl(timethylsilyl)ethynyl ether (30 mg, 0.145 mmol) andtetra-i-propoxytitanium (0.027 mL, 0.091 mmol) was addedi-propylmagnesium chloride (1.42 M diethyl ether solution, 0.144 mL,0.203 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into dark yellowish. The solutionwas kept stirred for 4 hours at −50° C. The solution kept at −50° C. wasgiven a diethyl ether solution (1 mL) containingp-toluene-sulfonylacetylene in powder form (16 mg, 0.087 mmol).

[0231] The reaction solution was heated to room temperature and wasstirred for 3 hours. The solution was given hydrochloric acid (1 mol/L)to suspend the reaction. The reaction product was extracted with diethylether. The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was analyzed indetail by ¹H NMR. It was found to contain no other isomers. The crudeproduct was purified by silica gel column chromatography(n-hexane-diethyl ether). There was obtained2,3-bis(cyclo-hexyloxy)-1,4-bis(trimethylsilyl)benzene (18 mg, 56%) inthe form of colorless oily substance.

[0232]¹H NMR: δ 0.28 (s, 18H, SiMe₃), 1.08-1.40 (m, 10H, cyclohexyl H),1.60 (symmetric m, 2H, cyclohexyl H), 1.75 (symmetric m, 4H, cyclohexylH), 1.86 (symmetric m, 4H, cyclohexyl H), 4.30 (tt, J=3.9, 10.5 Hz, 2H,O—CH, 7.05 (s, 2H, Ph-H).

[0233]¹³C NMR: δ 0.06 (SiMe₃), 24.82, 25.72, 32.69, 78.26 (O—C), 128.72(Ph), 135.61 (Ph), 153.35 (Ph).

[0234] IR (neat): 3060 (Ph), 2933, 2857, 1590, 1451, 1363, 1344, 1245,1221, 1196, 1177, 1127, 1043, 1019, 966, 887, 836, 758 cm⁻¹.

Example 17

[0235] 2,3-bis(cyclohexyloxy)-5-deuterio-1,4-bis(trimethylsilyl)-benzene

[0236] The same procedure as in Example 16 was repeated except thatheavy water was added for reaction before the addition of hydrochloricacid (1 mol/L). There was obtained2,3-bis(cyclohexyloxy)-5-deuterio-1,4-bis(trimethyl-silyl)benzene.

[0237]¹H NMR: δ 0.28 (s, 18H, SiMe₃), 1.08-1.40 (m, 10H, cyclohexyl H),1.60 (symmetric m, 2H, cyclohexyl H), 1.75 (symmetric m, 4H, cyclohexylH), 1.86 (symmetric m, 4H, cyclohexyl H), 4.30 (tt, J=3.9, 10.5 Hz, 2H,O—CH), 7.05 (s, 1H, Ph-H).

[0238] An introduction of 98% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.05 (Ph-H) of2,3-bis(cyclohexyloxy)-1,4-bis(trimethyl-silyl)benzene.

Example 18

[0239] 2,2-bis[(benzyloxy)methyl]-4,7-bis(trimethylsilyl)indan

[0240] To a diethyl ether solution (4.5 mL) containing4,4-bis[(benzyloxy)methyl]-1,7-bis(trimethylsilyl)-1,6-heptadiyne (50mg, 0.105 mmol) and tetra-i-propoxytitanium (0.039 mL, 0.131 mmol) wasadded i-propylmagnesium chloride (1.49 M diethyl ether solution, 0.197mL, 0.293 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into dark yellowish. The solutionwas kept stirred for 4 hours at −50° C. The solution (kept at −50° C.)was given a diethyl ether solution (1 mL) containingp-toluenesulfonylacetylene in powder form (23 mg, 0.126 mmol).

[0241] The reaction solution was heated to room temperature and wasstirred for 3 hours. The solution was given hydrochloric acid (1 mol/L)to suspend the reaction. The reaction product was extracted with diethylether. The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was purified bysilica gel column chromatography (n-hexane-diethyl ether). There wasobtained 2,2-bis[(benzyloxy)methyl]-4,7-bis(trimethyl-silyl)indan (39mg, 74%) in the form of colorless oily substance.

[0242]¹H NMR: δ 0.28 (s, 18H, SiMe₃), 2.90 (s, 4H, PhCH₂), 3.52 (s, 4H,CH₂OBn), 4.53 (s, 4H, PhCH₂O), 7.22-7.35 (m, 12H, Ph-H).

[0243]¹³C NMR: δ −0.97 (SiMe₃), 39.65, 47.69, 73.22, 73.44, 127.46 (Ph),127.55 (o- or m-Ph), 128.36 (m- or o-Ph), 131.29 (Ph), 136.87 (Ph),138.98 (Ph), 146.75 (Ph).

[0244] IR (neat): 3090 (Ph), 3060 (Ph), 3033 (Ph), 2953, 2895, 2852,1496, 1453, 1359, 1249 (SiMe₃), 1198, 1100, 1028, 892, 836, 751, 696cm⁻¹.

[0245] Elemental analysis: calculated (C₃₁H₄₂O₂Si₂): C, 74.05%; H,8.42%. found: C, 73.89%; H, 8.35%.

Example 19

[0246] N-benzyl-4,7-bis(trimethylsilyl)-1-isoindolinone

[0247] To a diethyl ether solution (1.5 mL) containingN-benzyl-N-[3-(trimethylsilyl)-2-propinyl]-3-(trimethyl-silyl)-2-propinamide(30 mg, 0.088 mmol) and tetra-i-propoxytitanium (0.039 mL, 0.132 mmol)was added i-propyl-magnesium chloride (1.48 M diethyl ether solution,0.179 mL, 0.263 mmol) at −78° C. under an argon stream. There wasobtained a homogenous yellowish solution. The solution was slowly heatedto −30° C. over 30 minutes. The solution turned into reddish. Thesolution was kept stirred for 4 hours at −30° C. The solution (kept at−30° C.) was given a diethyl ether solution (1 mL) containingp-toluenesulfonylacetylene (19 mg, 0.105 mmol) in powder form.

[0248] The reaction solution was heated to room temperature and wasstirred for 3 hours. The solution was given hydrochloric acid (1 mol/L)to suspend the reaction. The reaction product was extracted with diethylether. The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was purified bysilica gel column chromatography (n-hexane-ethyl acetate). There wasobtained N-benzyl-4,7-bis(trimethylsilyl)-1-isoindolinone (24 mg, 88%)in the form of colorless oily substance.

[0249]¹H NMR: δ 0.27 (s, 9H, SiMe₃), 0.44 (s, 9H, SiMe₃), 4.29 (s, 2H,PhCH₂N), 4.81 (s, 2H, PhCH₂N), 7.27-7.39 (m, 5H, Ph-H), 7.59 (d, J=7.2Hz, 1H, Ph-H), 7.63 (d, J=7.2 Hz, 1H, Ph-H).

[0250]¹³C NMR: δ −0.96 (SiMe₃), −0.61 (SiMe₃), 46.31, 50.49, 127.62(Ph), 128.09 (o- or m-Ph), 128.83 (m- or o-Ph), 133.70 (Ph), 135.09(Ph), 135.84 (Ph), 136.09 (Ph), 137.36 (Ph), 139.75 (Ph), 146.25 (Ph),169.59 (C═O).

[0251] IR (neat): 3050 (Ph), 3030 (Ph), 2953, 1688 (C═O), 1640, 1540,1496, 1452, 1410, 1358, 1320, 1293, 1250 (SiMe₃), 1193, 1028, 944, 919,840, 751, 696 cm⁻¹.

[0252] Elemental analysis: calculated (C₂₁H₂₉NOSi): C, 68.61%; H, 7.95%;N, 3.81%. found: C, 68.40%; H, 7.87%; N, 3.75%.

Example 20

[0253] 5-(t-butoxycarbonyl)-6-hexylindan

[0254] (1,6-heptadiynyl p-tolylsulfone)

[0255] First, 1,6-heptadiynyl p-tolylsulfone as a starting material wassynthesized according to the following scheme.

[0256]¹H NMR: δ 1.76 (quintet, J=6.9 Hz, 2H, alkyl H), 1.96 (t, J=2.4Hz, 1H, C≡CH), 2.25 (dt, J=2.4, 6.9 Hz, 2H, CH₂C≡CH), 2.46 (s, 3H,PhMe), 2.51 (t, J=6.9 Hz, 2H, CH₂C≡CSO₂Tol), 7.37 (d, J=8.4 Hz, 2H,Ph-H), 7.87 (d, J=8.4 Hz, 2H, Ph-H).

[0257]¹³C NMR: δ 17.65, 17.94, 21.80, 25.91, 69.77 (C≡C), 78.81 (C≡C),82.18 (C≡C), 95.71 (C≡C), 127.21 (o- or m-Ph), 129.79 (m- or o-Ph),138.78 (p-Ph), 145.08 (ipso-Ph).

[0258] IR (neat): 3289 (Ph), 3058 (Ph), 2940, 2201 (C≡C), 1595, 1431,1327 (S═O), 1158 (S═O), 1089, 1048, 814 cm⁻¹. Elemental analysis:calculated (C₁₄H₁₄O₂S): C, 68.26%; H, 5.73%. found: C, 67.93%; H, 5.53%.

[0259] To a diethyl ether solution (1.5 mL) containing t-butyl2-nonyonate (20 mg, 0.095 mmol) and tetra-i-propoxy-titanium (0.035 mL,0.119 mmol) was added i-propylmagnesium chloride (1.48 M diethyl ethersolution, 0.180 mL, 0.267 mmol) at −78° C. under an argon stream. Therewas obtained a homogenous yellowish solution. The solution was slowlyheated to −50° C. over 30 minutes. The solution turned into reddish. Thesolution was kept stirred for 5 hours at −50° C. The solution (kept at−50° C.) was given a diethyl ether solution (1 mL) containing1,6-heptadinyl p-tolylsulfone (19 mg, 0.076 mmol) and the solution wasstirred at −50° C. for 3 hours.

[0260] The reaction solution was heated to room temperature and wasstirred for 3 hours. The solution was given hydrochloric acid (1 mol/L)to suspend the reaction. The reaction product was extracted with diethylether. The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was purified bysilica gel column chromatography (n-hexane-diethyl ether). There wasobtained 5-(t-butoxycarbonyl)-6-hexylindan (17 mg, 74%) in the form ofcolorless oily substance.

[0261]¹H NMR: δ 0.88 (t, J=6.9 Hz, 3H, Me), 1.20-1.55 (m, 8H, alkyl H),1.58 (s, 9H, C(CH₃)₃), 2.06 (quintet, J=7.2 Hz, 2H, cyclopentyl H), 2.86(t, J=7.2 Hz, 2H, PhCH₂), 2.88 (t, J=7.2 Hz, 4H, PhCH₂), 7.06 (s, 1H,Ph-H), 7.58 (s, 1H, Ph-H).

[0262]¹³C NMR: δ 13.98, 22.52, 25.35, 28.15 (C(CH₃)₃), 29.41, 31.75,32.14, 32.20, 32.76, 34.32, 80.70 (CO₂C), 125.91 (Ph), 126.56 (Ph),130.04 (Ph), 141.65 (Ph), 141.75 (Ph), 147.89 (Ph), 168.27 (C═O).

[0263] IR (neat): 3005 (Ph), 2960, 2927, 2845, 1716 (C═O), 1458, 1390,1366, 1278, 1255, 1167, 1118, 1022, 885, 856, 800 cm⁻¹.

[0264] Elemental analysis: calculated (C₂₀H₃₀O₂): C, 79.42%; H, 10.00%.found: C, 79.19%; H, 10.10%.

Example 21

[0265] 5-(t-butoxycarbonyl)-4-deuterio-6-hexylindan

[0266] The same procedure as in Example 20 was repeated except thatheavy water was added for reaction before the addition of hydrochloricacid (1 mol/L). There was obtained5-(t-butoxycarbonyl)-4-deuterio-6-hexylindan.

[0267]¹H NMR: δ 0.88 (t, J=6.9 Hz, 3H, Me), 1.20-1.55 (m, 8H, alkyl H),1.58 (s, 9H, C(CH₃)₃), 2.06 (quintet, J=7.2 Hz, 2H, cyclopentyl H), 2.86(t, J=7.2 Hz, 2H, PhCH₂), 2.88 (t, J=7.2 Hz, 4H, PhCH₂), 7.06 (s, 1H,Ph-H).

[0268] An introduction of 91% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.58 (Ph-H) of5-(t-butoxycarbonyl)-6-hexylindan.

Examples 22 and 23

[0269] The same procedure as in Example 20 was repeated to give thefollowing compounds except that the acetylene compound and diynecompound were replaced. TABLE 1

Example R¹ R² Z Yield (%) 22 CO₂Et Me CH₂C(CH₂OBn)₂CH₂ 60 23 CONEt₂C₆H₁₃ (CH₂)₃ 73

Example 24

[0270] 3,4-dibutylphenyl p-tolylsulfoxide

[0271] To a diethyl ether solution (1.5 mL) containing 5-decyne (0.020mL, 0.111 mmol) and tetra-i-propoxytitanium (0.041 mL, 0.139 mmol) wasadded i-propylmagnesium chloride (1.35 M diethyl ether solution, 0.231mL, 0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution (kept at −50° C.) wasgiven a diethyl ether solution (1 mL) containingp-toluenesulfinylacetylene (37 mg, 0.223 mmol) and the solution wasstirred at −50° C. for 1 hour.

[0272] The reaction solution was heated to −20° C. and then stirred for7 hours. The solution was given hydrochloric acid (1 mol/L) to suspendthe reaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-ethyl acetate).There was obtained 3,4-dibutylphenyl p-tolylsulfoxide (18 mg, 50%) inthe form of colorless oily substance.

[0273]¹H NMR: δ 0.91 (t, J=7.2 Hz, 3H, Me), 0.92 (t, J=7.2 Hz, 3H, Me),1.36 (sextet, J=7.2 Hz, 4H, alkyl H), 1.45-1.60 (m, 4H, alkyl H), 2.35(s, 3H, PhMe), 2.58 (t, J=7.2 Hz, 2H, PhCH₂), 2.61 (t, J=7.2 Hz, 2H,PhCH₂), 7.19 (d, J=8.1 Hz, 1H, Ph-H), 7.25 (d, J=8.1 Hz, 2H, Ph-H), 7.30(dd, J=1.8, 8.1 Hz, 1H, Ph-H), 7.43 (d, J=1.8 Hz, 1H, Ph-H), 7.52 (d,J=8.1 Hz, 2H, Ph-H).

[0274]¹³C NMR: δ 13.81 (2 peaks), 21.27, 22.58, 22.64, 32.19, 32.27,32.96, 33.05, 122.34 (Ph), 125.00 (o- or m-Ph), 125.44 (Ph), 129.98 (m-or o-Ph), 130.08 (Ph), 141.37 (Ph), 142.12 (Ph), 142.64 (Ph), 142.84(Ph), 144.20 (Ph).

[0275] IR (neat): 3033 (Ph), 2959, 2925, 2862, 1735, 1720, 1655, 1595,1458, 1400, 1380, 1305, 1090, 1048 (S═O), 970, 808 cm⁻¹.

Example 25

[0276] t-butyl 5-hexyl-4-methyl-2-(trimethylsilyl)benzoate

[0277] To a diethyl ether solution (3 mL) containing t-butyl3-(trimethylsilyl)-2-propinoate (50 mg, 0.252 mmol) andtetra-i-propoxytitanium (0.093 mL, 0.315 mmol) was addedi-propylmagnesium chloride (1.47 M diethyl ether solution, 0.480 mL,0.706 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution (kept at −50° C.) was given1-octyne (0.030 mL, 0.202 mmol), and the solution was stirred for 3hours.

[0278] The solution was given propargylbromide (0.028 mL, 0.378 mmol).The reaction solution was heated to room temperature and stirred for 4hours at room temperature. The solution was given hydrochloric acid (1mol/L) to suspend the reaction. The reaction product was extracted withdiethyl ether. The organic layer was washed with an aqueous solution ofsodium bicarbonate and then dried with anhydrous sodium sulfate. Thesolvent was distilled away under reduced pressure. There was obtained acrude product in the form of oily substance. The crude product underwentpreparative silica gel thin-layer chromatography (n-hexane-diethylether). There was obtained t-butyl5-hexyl-4-methyl-2-(trimethylsilyl)benzoate (37 mg, 52%) in the form ofcolorless oily substance.

Examples 26 and 27

[0279] The same procedure as in Example 25 was repeated to give thefollowing compounds except that the acetylene compound was replaced.TABLE 2

Example R¹ R² R⁴ A B 26 SiMe₃ CO₂t-Bu

— 53% 27 SiMe₃ C₆H₁₃ (CH₂)₂OBn 35% —

Example 28

[0280] The same procedure as in Example 27 was repeated except thatheavy water was added for reaction before the addition of hydrochloricacid (1 mol/L). There was obtained a compound represented by the formulabelow in which deuteration took place at the benzyl position.Incidentally, the ratio of introduction of deuterium was quantitative.

Example 29

[0281] 2,2-bis[(benzyloxy)methyl]-5-methyl-4,7-bis(trimethylsilyl)-indan

[0282] To a diethyl ether solution (2 mL) containing4,4-bis[(benzyloxy)methyl]-1,7-bis(trimethylsilyl)-1,6-heptadiyne (50mg, 0.104 mmol) and tetra-i-propoxytitanium (0.039 mL, 0.131 mmol) wasadded i-propylmagnesium chloride (1.53 M diethyl ether solution, 0.185mL, 0.282 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution was kept stirred for 4 hours at −50° C.The solution (kept at −50° C.) was given propargylbromide (0.012 mL,0.157 mmol).

[0283] The reaction solution was heated to room temperature and stirredfor 4 hours. The solution was given hydrochloric acid (1 mol/L) tosuspend the reaction. The reaction product was extracted with diethylether. The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product underwentpreparative silica gel thin-layer chromatography (n-hexane-diethylether). There was obtained2,2-bis[(benzyloxy)methyl]-5-methyl-4,7-bis(trimethylsilyl)indan (40 mg,73%) in the form of colorless oily substance.

Examples 30 to 34

[0284] The same procedure as in Example 29 was repeated to give thefollowing compounds except that the acetylene compound or electrophilicreagent was replaced. TABLE 3

Electrophilic Yield Example R⁵ X⁶ reagent Q (%) 30 H Cl H⁺ CH₃ 60 31 MeBr H⁺ CH₃ 31 32 H Br I₂

72 33 H Br O₂

43 34 H Br ≡—CH₂Br/Cu⁺

42

Example 35

[0285] N,N-diethyl-3-hexyl-5-phenyl-2-picolinamide

[0286] To a diethyl ether solution (1.5 mL) containingN,N-diethyl-2-nonyneamide (48 mg, 0.229 mmol) andtetra-i-propoxytitanium (0.084 mL, 0.285 mmol) was addedi-propyl-magnesium chloride (1.53 M diethyl ether solution, 0.418 mL,0.637 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution (kept at −50° C.) was givenethynylbenzene (0.020 mL, 0.182 mmol). The solution was stirred for 3hours.

[0287] Then, the solution was given p-toluenesulfonylcyanide (49 mg,0.273 mmol) in powder form. The solution was stirred at −50° C. for 3hours and then given water to suspend the reaction. The solution wasgiven anhydrous sodium sulfate. Precipitates were filtered off throughCelite, and the solvent was distilled away under reduced pressure. Therewas obtained a crude product in the form of oily substance. The crudeproduct was purified by silica gel column chromatography (n-hexane-ethylacetate). There was obtained N,N-diethyl-3-hexyl-5-phenyl-2-picolinamide(43 mg, 70%) in the form of colorless oily substance.

Example 36

[0288] N,N-diethyl-3-hexyl-5-phenyl-6-iodo-2-picolinamide

[0289] The same procedure as in Example 35 was repeated except thatiodine was added before water was added to suspend the reaction. Therewas obtained N,N-diethyl-3-hexyl-5-phenyl-6-iodo-2-picolinamide in a 70%yield.

Examples 37 to 40

[0290] The same procedure as in Example 35 was repeated to give thefollowing compounds except that the acetylene compound was replaced andthe reaction temperature (for reaction of p-toluenesulfonecyanide) waschanged. TABLE 4

Reaction temperature Example R¹ R² R⁴ (° C.) A B 37 CONEt₂ C₆H₁₃ C₆H₁₃−50 — 63% 38 CONEt₂ C₆H₁₃ SiMe₃ −50 — 55% 39 CO₂t-Bu C₆H₁₃ C₆H₁₃ −50 —28% 40 CO₂t-Bu C₆H₁₃ C₆H₁₃ −10 — 50%

Example 41

[0291] 2-[2-(benzyloxy)ethyl]-4,5-dibutylpyridine

[0292] To a diethyl ether solution (1.5 mL) containing 5-decyne (0.020mL, 0.111 mmol) and tetra-i-propoxytitanium (0.041 mL, 0.139 mmol) wasadded i-propylmagnesium chloride (1.36 M diethyl ether solution, 0.229mL, 0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 3 hours at −50° C. The solution (kept at −50° C.) wasgiven a diethyl ether solution (1 mL) of 4-benzyloxy-1-butyne (14 mg,0.089 mmol). The solution was stirred for 2 hours.

[0293] Then, the solution was given a diethyl ether solution (1 mL)containing p-toluenesulfonylcyanide in powder form (24 mg, 0.134 mmol).The reaction solution was heated to −10° C. The solution was stirred at−10° C. for 3 hours and then given water to suspend the reaction. Thesolution was given anhydrous sodium sulfate. Precipitates were filteredoff through Celite, and the solvent was distilled away under reducedpressure. There was obtained a crude product in the form of oilysubstance. The crude product was purified by silica gel columnchromatography (n-hexane-ethyl acetate). There was obtained2-[2-(benzyloxy)ethyl]-4,5-dibutyl-pyridine (16 mg, 55%) in the form ofcolorless oily substance.

[0294] The present invention permits efficient production of anorganotitanium compound capable of regioselectively converting asubstituted acetylene compound into polysubstituted benzene orpolysubstituted pyridine. The present invention also permits efficientproduction of a variety of polysubstituted benzene and polysubstitutedpyridine useful for pharmaceuticals and agricultural chemicals andintermediates thereof by various addition reactions on the titaniumcompound.

1. A process for producing an organotitanium compound which comprisesreacting an acetylene compound represented by the formula (1) below inthe presence of a titanium compound represented by the formula (2) belowand a Grignard reagent represented by the formula (3) below with anacetylene compound represented by the formula (4) below and furtherreacting with a compound represented by the formula (5) below, therebygiving said titanium compound represented by the formula (6) and/or (7)below.

[where R¹ and R² denote mutually independently a C₁₋₂₀ alkyl group{which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkylaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).] TiX¹X²X³X⁴   (2) [where X¹, X², X³, and X⁴ denote mutuallyindependently a halogen atom, C₁₋₆ alkoxy group {which may besubstituted with a phenyl group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenyl group) or naphthyl group},phenoxy group (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆alkoxy group, or phenyl group), or naphthoxy group.] RMgX⁵   (3) [whereR denotes a C₂₋₈ alkyl group having a hydrogen atom at the β position,and X⁵ denotes a halogen atom.]

[where R³ and R⁴ denote mutually independently a hydrogen atom, C₁₋₂₀alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkylamino-carbonyl group, phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R¹² (where R¹⁰,R¹¹, and R¹² are defined as above).]

[where R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group) or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ group {where R⁶ denotes a C₁₋₆ alkylgroup or phenyl group (which may be substituted with a halogen atom orC₁₋₆ alkyl group) and n denotes 1 or 2}, OSO₂R⁶ group (where R⁶ isdefined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkylgroup); and m denotes 0 or 1.]

[where R¹˜R⁵, Z, X⁶, and m are defined as above; and X^(p) and X^(q)denote any of X¹˜X⁴ (which are defined as above).]
 2. A process forproducing an organotitanium compound which comprises reacting anacetylene compound represented by the formula (8) below in the presenceof a titanium compound represented by the formula (2) below and aGrignard reagent represented by the formula (3) below with a compoundrepresented by the formula (5) below, thereby giving said titaniumcompound represented by the formula (9) and/or (10) below.

[where R¹ denotes a C₁₋₂₀ alkyl group {which may be substituted with aC₁₋₆ alkoxy group (which may be substituted with a phenyl group) orOSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆alkyl group or phenyl group)}, C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkyaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denote mutuallyindependently a halogen atom, C₁₋₆ alkyl group, or phenyl group); R⁴denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylamino-carbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylamino-carbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² are defined as above);and Y denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷ {where Z¹, Z³, Z⁴, Z⁵, and Z⁷denote mutually independently C═O or CR¹⁴R¹⁵

where R¹⁴ and R¹⁵ denote mutually independently a hydrogen atom or C₁₋₆alkyl group (which may be substituted with a C₁₋₆ alkoxy group (whichmay be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, andR⁹ are defined as above))

, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶

where R¹⁶ denotes a C₁₋₆ alkyl group (which may be substituted with aC₁₋₆ alkoxy group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))

, or CR^(14′)R^(15′)

where R^(14′) and R^(15′) denote mutually independently a hydrogen atomor C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))

}.] TiX¹X²X³X⁴   (2) [where X¹, X², X³, and X⁴ denote mutuallyindependently a halogen atom, C₁₋₆ alkoxy group {which may besubstituted with a phenyl group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenyl group), or a naphthyl group)},phenoxy group (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆alkoxy group, or phenyl group), or naphthoxy group.] RMgX⁵   (3) [whereR denotes a C₂₋₈ alkyl group having a hydrogen atom at the β position,and X⁵ denotes a halogen atom.]

[where R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, and phenyl group), or naphthyl group}, phenoxy group (which maybe substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ {where R⁶ denotes a C₁₋₆ alkyl groupor phenyl group (which may be substituted with a halogen atom or C₁₋₆alkyl group) and n denotes 1 or 2}, OSO₂R⁶ (where R⁶ is defined asabove), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkyl group);and m denotes 0 or 1.]

[where R¹, R⁴, R⁵, Y, Z, X⁶, and m are defined as above; and X^(p) andX^(q) denote any of X¹˜X⁴ (which are defined as above).]
 3. A processfor producing an organotitanium compound which comprises reacting anacetylene compound represented by the formula (1) below in the presenceof a titanium compound represented by the formula (2) below and aGrignard reagent represented by the formula (3) below with a compoundrepresented by the formula (11) below, thereby giving said titaniumcompound represented by the formula (12) below.

[where R¹ and R² denote mutually independently a C₁₋₂₀ alkyl group{which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkyaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹-R¹² (where R¹⁰,R¹¹, and R¹² denote mutually independently a halogen atom, C₁₋₆ alkylgroup, or phenyl group).] TiX¹X²X³X⁴   (2) [where X¹, X², X³, and X⁴denote mutually independently a halogen atom, C₁₋₆ alkoxy group {whichmay be substituted with a phenyl group (which may be substituted with aC₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group), or a naphthylgroup}, phenoxy group (which may be substituted with a C₁₋₆ alkyl group,C₁₋₆ alkoxy group, or phenyl group), or naphthoxy group).] RMgX⁵   (3)[where R denotes a C₂₋₈ alkyl group having a hydrogen atom at the βposition, and X⁵ denotes a halogen atom.]

[where R³ denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylamino-carbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylamino-carbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² are defined as above);R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group (whichmay be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Y′ denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷{where Z¹, Z³, Z ⁴, Z⁵, and Z⁷ denote mutually independently C═O orCR¹⁴R¹⁵

where R¹⁴ and R¹⁵ denote mutually independently a hydrogen atom or C₁₋₆alkyl group (which may be substituted with a C₁₋₆ alkoxy group (whichmay be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, andR⁹ are defined as above))

, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶

where R¹⁶ denotes a C₁₋₆ alkyl group (which may be substituted with C₁₋₆alkoxy group (which may be substituted with a phenyl group)) orOSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined as above)

, or CR^(14′)R^(15′)

where R^(14′) and R^(15′) denote mutually independently a hydrogen atom,C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))

}; X⁶ denotes a halogen atom, C₁₋₆ alkoxy group {which may besubstituted with a phenyl group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenyl group), or naphthyl group},phenoxy group (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆alkoxy group, or phenyl group), naphthoxy group, SO_(n)R⁶ {where R⁶denotes a C₁₋₆ alkyl group or phenyl group (which may be substitutedwith a halogen atom or C₁₋₆ alkyl group), and n denotes 1 or 2}, OSO₂R⁶(where R⁶ is defined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotesa C₁₋₆ alkyl group); and m denotes 0 or 1.]

[where R¹ to R³, R⁵, Y′ , X⁶, and m are defined as above; and X^(p) andX^(q) denote any of X¹˜X⁴ (which are defined as above).]
 4. A processfor producing an organotitanium compound which comprises reacting anacetylene compound represented by the formula (1) below in the presenceof a titanium compound represented by the formula (2) below and aGrignard reagent represented by the formula (3) below with a compoundrepresented by the formula (13) below, thereby giving said titaniumcompound represented by the formula (14) below.

[where R¹ and R² denote mutually independently a C₁₋₂₀ alkyl group{which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkyaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).] TiX¹X²X³X⁴   (2) [where X¹, X², X³, and X⁴ denote mutuallyindependently a halogen atom, C₁₋₆ alkoxy group fwhich may besubstituted with a phenyl group {which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenyl group) or naphthyl group},phenoxy group (which may be substituted with a C₆ alkyl group, C₁₋₆alkoxy group, or phenyl group), or naphthoxy group.] RMgX⁵   (3) [whereR denotes a C₂₋₈ alkyl group having a hydrogen atom at the β position,and X⁵ denotes a halogen atom.]

[where R′ denotes a hydrogen atom or C₁₋₂₀ alkyl group; and X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group) or naphthyl group), phenoxy group (which may besubstituted with C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group),naphthoxy group, SO_(n)R⁶ group {where R⁶ denotes a C₁₋₆ alkyl group orphenyl group (which may be substituted with a halogen atom or C₁₋₆ alkylgroup), and n denotes 1 or 2}, OSO₂R⁶ (where R⁶ is defined as above), orOP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkyl group).]

[where R¹, R², R′ , Z, and X⁶ are defined as above; and X^(p) and X^(q)denote any of X¹ to X⁴ (which are defined as above).]
 5. A process forproducing an organotitanium compound as defined in any of claims 1 to 4,wherein the titanium compound is tetra-i-propoxytitanium.
 6. A processfor producing an organotitanium compound as defined in any of claims 1to 5, wherein the Grignard reagent is an i-propyl Grignard reagent.
 7. Aprocess for addition reaction which comprises adding to theorganotitanium compound obtained by the process defined in any of claims1 to 6 a compound having an electrophilic functional group or anelectrophilic reagent, and performing addition reaction on theorganotitanium compound.
 8. A process for addition reaction as definedin claim 7, wherein the electrophilic functional group is an aldehydegroup, ketone group, imino group, hydrazone group, aliphatic doublebond, aliphatic triple bond, acyl group, ester group, or carbonategroup.
 9. A process for addition reaction as defined in claim 7, whereinthe electrophilic reagent is water, heavy water, chlorine, bromine,iodine, N-bromosuccinimide, oxygen, carbon dioxide gas, or carbonmonoxide.